Biswal et al. BMC Plant Biology          (2022) 22:542  
https://doi.org/10.1186/s12870-022-03932-y
REVIEW Open Access
Maize Lethal Necrosis disease: review 
of molecular and genetic resistance 
mechanisms, socio-economic impacts, 
and mitigation strategies in sub-Saharan Africa
Akshaya Kumar Biswal1*  , Amos Emitati Alakonya1, Khondokar Abdul Mottaleb1, Sarah J. Hearne1, Kai Sonder1, 
Terence Luke Molnar2, Alan M. Jones3, Kevin Vail Pixley1 and Boddupalli Maruthi Prasanna4 
Abstract 
Background: Maize lethal necrosis (MLN) disease is a significant constraint for maize producers in sub-Saharan Africa 
(SSA). The disease decimates the maize crop, in some cases, causing total crop failure with far-reaching impacts on 
regional food security.
Results: In this review, we analyze the impacts of MLN in Africa, finding that resource-poor farmers and consumers 
are the most vulnerable populations. We examine the molecular mechanism of MLN virus transmission, role of vectors 
and host plant resistance identifying a range of potential opportunities for genetic and phytosanitary interventions to 
control MLN. We discuss the likely exacerbating effects of climate change on the MLN menace and describe a sober-
ing example of negative genetic association between tolerance to heat/drought and susceptibility to viral infection. 
We also review role of microRNAs in host plant response to MLN causing viruses as well as heat/drought stress that 
can be carefully engineered to develop resistant varieties using novel molecular techniques.
Conclusions: With the dual drivers of increased crop loss due to MLN and increased demand of maize for food, the 
development and deployment of simple and safe technologies, like resistant cultivars developed through acceler-
ated breeding or emerging gene editing technologies, will have substantial positive impact on livelihoods in the 
region. We have summarized the available genetic resources and identified a few large-effect QTLs that can be further 
exploited to accelerate conversion of existing farmer-preferred varieties into resistant cultivars.
Keywords: Maize, MLN, MCMV, SCMV, Potyvirus, Drought stress, Gene editing, QTL
Background deformed seeds, thereby lowering the yield drastically 
Maize Lethal Necrosis (MLN) or corn lethal necro- [1–3]. A wide range of crop losses from MLN have been 
sis disease poses a severe threat to maize (Zea mays L.) reported, and a recent simulation predicted up to 73% 
production. Maize plants with MLN disease are often of grain loss for susceptible varieties [4]. Discovery of 
barren; the ears formed are small with no or a few germplasm carrying resistance to MLN disease has led 
to development and release of hybrids that are resistant/
tolerant to the causal viruses. Despite considerable suc-
*Correspondence:  a.k.biswal@cgiar.org cess of these efforts, MLN remains a threat to the food 
1 International Maize and Wheat Improvement Center (CIMMYT), Km. 45, and feed requirements of resource-poor farmers of sub-
Carretera Mexico-Veracruz, El Batan, Texcoco C.P. 56237, Mexico Saharan Africa (SSA) given the possibility of viruses to 
Full list of author information is available at the end of the article
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Biswal et al. BMC Plant Biology          (2022) 22:542 Page 2 of 21
develop new variants with potential to bypass host plant maize consumers, commercial seed sector, millers and 
resistance. transporters who engage in the maize value chain in sev-
Maize is critical for food security in Africa, providing, eral ways.
for example, ~ 25% of the total dietary energy intake in MLN was first observed in Peru in 1973 [7, 8] and 
eastern African countries including Kenya [5, 6]. Maize later in the USA in 1976 [2, 3]. In 2011, MLN was first 
kernels are consumed off the cob, roasted, cooked, and reported in south-western Kenya [1]. MLN-affected plots 
most commonly processed into a variety of products recorded yield loss worth US$ 53.2 million in 2012, $180 
from maize flour. Because millions of small-scale farm- million in 2013 and $198 million in 2014 respectively [9, 
ers rely on maize to feed their families, any drop in maize 10]. MLN disease was confirmed in six other African 
yield threatens to food security and livelihoods. Other countries within three subsequent years (Fig. 1). Follow-
stakeholders at risk from MLN include resource-poor ing the identification of a strong source of resistance in an 
Fig. 1 Intensity of maize cultivation and distribution of MLN disease in selected countries of Africa. Data Sources: FAO [14], SPAM 2010 [15],  
CIMMYT [16]
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 3 of 21
inbred line from Thailand, marker-assisted backcrossing biotechnologists, and other stakeholders for efforts 
was used to convert susceptible lines to resistant and to towards developing tolerant/resistant varieties to ensure 
deploy an initial set of 18 MLN resistant/tolerant hybrids food security in sub-Saharan Africa.
in east African countries [11]. However, a recent survey 
in key maize seed production zones of Kenya indicated Transmission of MLN pathogens
that at least 70% of seeds were infected with one or both MLN has mainly been associated with co-infection of 
of MLN causing viruses (MCMV and SCMV), indicating MCMV and SCMV in Africa, although one study has 
that maize production remains under threat from MLN associated it with MCMV and JGMV [22]. A recent 
[12]. Given the recent Russian invasion into Ukraine, metagenomic analysis indicated that MCMV is the most 
the impact of production constraints including MLN prevalent virus associated with MLN in Kenya, while 
are more acute and knock-on challenges to agricultural SCMV is the second [23].
commodity markets, which may affect many countries, in 
particular, those were more reliant upon its agricultural Vector transmission of MLN causing viruses
exports. Among these, the hardest hit countries have MCMV can be transmitted by maize thrips (F. willianmsi) 
been predicted to be the ones in Africa [13]. [24, 25], western flower thrips (F. occidentalis) [26], bee-
Manifestation of MLN disease is based upon a syner- tles and root worms [27] (Fig. 2). Thrips are reported to 
gistic infection of a machlomovirus, maize chlorotic mot- transmit MCMV for a semipersistent period of 6  days 
tle virus (MCMV), with any one of several potyviruses, after acquiring it [24]. MCMV is relatively new to Africa 
namely sugarcane mosaic virus (SCMV), maize dwarf [1], while SCMV has been on the continent for a longer 
mosaic virus (MDMV), wheat streak mosaic virus time, probably introduced on infected root cane (sug-
(WSMV), or Johnson grass mosaic virus (JGMV) [2, 17, arcane) and maize seed [28]. SCMV and MDMV, like a 
18]. Maize yellow mosaic virus (MYMV) has also been majority of potyviruses, are non-persistently transmitted 
found in plants infected with MLN, but its direct role, by several aphids that are widely distributed where maize 
if any, in MLN is unascertained to date [19]. MLN dis- is cultivated. It is estimated that aphids disseminate about 
ease affects maize plants throughout all developmental 200 species (~ 28%) of vector-transmitted plant viruses 
stages [3]. Leaves of infected plants show chlorotic mot- [29] and hence control of aphids alone can significantly 
tle that starts from the base of the younger leaf in the restrict the invasion of MLN and many other diseases 
whorl and extends upwards or starts from the leaf mar- into maize fields. WSMV, which is transmitted by wheat 
gins progressing inward [3]. Necrosis of youngest leaf, in curl mite in a semipersistent manner, can lead to MLN 
some cases, lead to “dead hearts” and plant death before disease symptoms in maize coinfected with MCMV. 
tasseling [1]. In maturing plants, MLN causes necrosis However, WSMV is not a major pathogen of maize due 
in the tassel that progresses downwards [3]. MLN infec- to genetic resistance and it has not been reported in East 
tion also causes dwarfing and premature aging of maize Africa or Asia [18, 21].
plants [20]. Plants resistant to one of the viruses can also Virus transmission relies on interaction between spe-
develop disease symptoms due to complex interactions cific receptors in the gut of the insect vector and virus 
among other virulent viruses [21]. With predicted cli- coat proteins [30]. For example, potyvirus helper com-
mate change, maize cropping will be increasingly threat- ponent-proteinase (HC-Pro) forms a bridge between 
ened by abiotic stresses such as drought and heat stress. the viral coat protein (CP) and certain receptors in the 
Most of the abiotic stress-tolerant maize lines, which insect stylet to facilitate the virion retention and trans-
have been deployed in Africa in hybrid combinations are mission [31]. Vectors can also be induced by acquired 
susceptible to MLN. However, a few maize hybrids with viruses to change their feeding behavior, resulting in 
resistance or tolerance to MLN coupled with drought tol- higher transmission rates to selected hosts [32]. Because 
erance have recently been deployed in east Africa [11]. both MCMV and SCMV are insect-transmitted, it might 
In this article, we: 1) review the biological and genetic be useful to understand if and how they interact with the 
understanding of MLN disease; 2) explore factors influ- vector system. For instance, does the feeding behavior 
encing its spread and severity; 3) highlight disease of the insect vectors change after acquiring one or more 
mitigation options, focusing on current and potential MLN causal viruses? What happens when more than 
germplasm-based contributions, including the potential one virus is acquired by a single insect vector? Currently, 
of genome editing to accelerate development of novel there is more focus on understanding how viruses under 
resistant germplasm; and 4) examine the socio-economic mixed infections interact in host plants than in the vec-
impacts of the disease on major maize consuming coun- tors [33, 34]. It is important to understand interactions of 
tries in eastern Africa. The data driven strategies out- mixed viral infections not just in hosts but also in trans-
lined in this review are immensely valuable for breeders, mitting vectors that also have endogenous RNA silencing 
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 4 of 21
Fig. 2 Transmission of MLN causing viruses. At the center, we have a maize plant that is amenable to infection by any of the four potyviruses on 
the right and MCMV on the left. The model further shows the main grass family members acting as reservoirs of the four important potyviruses 
(SCMV, MDMV, JGMV and WSMV) linked to MLN with aphids acting as the main transmitting vectors and a wheat curl mite transmitting only WSMV. 
Different dispersal mechanisms of MCMV ranging from transmission by thrips, beetles and rootworms has been presented on the left. Further, it lists 
mechanical, soil residues and contaminated seed as important transmission mechanisms of MCMV while the role of irrigation water and nematodes 
remain questionable
mechanisms [35]. Such knowledge may suggest manage- inoculation has proved that different natural and planted 
ment approaches that manipulate the vector systems to grass species, such as Bromus spp., Digitaria sangui-
the detriment of viruses, they transmit [31]. nalis, Eragrostis trichodes, Hordeum spp., Panicum spp., 
Setaria spp., Sorghum spp. and Triticum aestivum can be 
Reservoirs of MLN causing viruses infected by either or both MCMV and SCMV [6]. In con-
Green-bridge or overlapping cropping cycles of viral trast to previous studies, MCMV and SCMV were both 
host species promote the spread of MLN disease through recently detected in a dicot plant Commelina bengha-
insect vectors. Avoiding green-bridges can reduce lensis belonging to family Commelinaceae, highlighting 
populations of insect vectors and consequently limit the need to screen the host range of MLN causal viruses 
the spread of the disease from one season to another. outside the generally accepted monocot niche [39].
Observing a non-cropping season of 60  days for maize Several cultural practices have been proposed to aid 
or any reservoir species has been shown to reduce inci- in lowering MCMV and other MLN causing virus inci-
dence of MCMV [18]. This is important since MLN caus- dence, including non-cropping fallow periods, crop rota-
ing viruses can reside in non-maize hosts such as weeds tion with non-host plants, and sanitary practices such 
occurring in same agroecosystem [25]. Reducing or elim- as use of clean equipment and getting rid of plant resi-
inating weedy viral host species in maize fields can also dues in fields [17]. Soil containing MCMV-infected crop 
reduce MLN incidence [36]. residue has been shown to spread MCMV to subsequent 
The natural host range of MCMV is restricted to the cropping seasons. Further, the longevity of existence of 
Poaceae family and includes Sorghum bicolor, Hordeum MLN-causal viruses in the soil remains unknown. Such 
vulgarae, Triticum aestivum, Panicum millaceu and Sac- information could inform recommendations about effec-
charum officinarrum [37], although some Poaceae fam- tive non-cropping periods and cultural practices, dis-
ily members are reportedly immune [38]. Mechanical cussed in this section, which would need to be balanced 
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 5 of 21
with other husbandry practices targeting soil fertility, infection by SCMV and MCMV, it is unknown what hap-
organic carbon and water management. The disease may pens to expression of ZmElc in that case and how the 
also be transmitted through infected maize seeds [40]. growth of both viruses is supported. Knock down of 
Diverse MCMV isolates have been detected  in maize ZmElc expression under SCMV infection also decreases 
seeds [41]. Therefore, usage of virus-free seeds is impor- the expression of another maize susceptibility fac-
tant in controlling MLN in the African continent. Trans- tor eIF4E that promotes infection of both MCMV and 
mission of SCMV via seed or spread of potyviruses from SCMV. Though SCMV VPg interacts with both ZmElc 
infected sugarcane fields near maize fields are not con- and eIF4E, no direct interaction has been detected 
sidered major risks, because potyviruses responsible for between ZmElc and eIF4E [46].
MLN are endemic in maize growing areas worldwide. The virus induced perturbation of maize chloroplast 
structure and function has been linked to ferredoxin-5 
Molecular mechanism of the disease progression (Fd V)  that interacts with SCMV HC-Pro protein [48]. 
and resistance Proteins of potyvirus also exploit the host machinery for 
As plants are sessile, most plant viruses are transmitted their post-translational modification such as SUMOyla-
by insect vectors that feed on the host plant and establish tion, which increases their virulence [49]. Since eukary-
an entry point by creating a wound. Upon entering the otic systems generally carry families of genes with 
host, viruses employ a handful of their genes to orches- redundant functions, mutation in one or more of these 
trate host cells’ machinery to copy their genetic material genes that are not essential for the plant survival can pro-
resulting in replication of new virus particles while at the vide resistance to viral infection.
same time circumventing the host’s defense mechanism. 
Some of the viral proteins mediate cell-to-cell movement Interaction between MLN causing viruses and the host 
of viral particles to facilitate spread of infection to differ- plant
ent plant parts through host plants’ transport streams. More than 50 viruses naturally infect maize [37]. Though 
many viral diseases are caused by single viruses, mixed 
General mechanism of viral infection viral infection of plants, as is the case for MLN, is also 
The establishment of viral infection is determined by common in nature. Sometimes infection by one virus 
the availability of host factors or susceptibility genes suppresses the introduction of the other. Alternatively, 
necessary for virus replication and movement. The dis- presence of the first may facilitate co-infection by the 
ease severity is the resultant effect of plant defense to second, while in some instances both viruses may co-
the causal virus(es) and viral suppression of host plant’s exist without affecting one another [29].
defense responses [42]. For example, host factors such as The MCMV combines with one of the members of 
components of the maize brassinosteroid (BR) pathway the Potyviridae family to cause the catastrophic MLN 
induce the susceptibility of maize to MCMV infection disease [2, 3]. Typically, potyviruses enhance the titer of 
[43]. Proteomic analysis has determined that disulfide the partner virus [50]. The co-infection of MCMV and 
isomerases like protein ZmPDIL-1 and peroxiredoxin SCMV has shown higher accumulation of MCMV parti-
family protein ZmPrx5 also enhance host susceptibil- cles than single infection by MCMV, though SCMV titer 
ity to MCMV [44]. Class I β-1,3-glucanase (GluI), asso- remains similar between single and double infection [51]. 
ciated with plasmodesmatal size exclusion, is known to The accumulation of MCMV is dependent on a potyvi-
promote plant virus movement [45]. Maize Elongin C ral silencing suppressor known as the helper-component 
(ZmElc) is another host factor that interacts with SCMV protease (HC-Pro). Synergistic infection of MCMV and 
VPg and facilitates virus infection [46]. The ZmElc gene SCMV could significantly increase the accumulation 
expression is upregulated post-SCMV infection. It also of virus-derived small interfering RNAs (vsiRNAs) of 
interacts with VPg of other members of the genus Poty- MCMV that can potentially target dozens of host genes 
virus such as pennisetum mosaic virus (PenMV) and [51, 52]. This raises the question of whether a specific-
tobacco vein banding mosaic virus (TVBMV) indicating structured single-stranded RNA in SCMV-like potyvi-
that ZmElc may be a common maize susceptibility fac- ruses promotes production of MCMV vsiRNAs.
tor for potyvirus infection. However, overexpression of Viral pathogens can influence the host-vector interac-
ZmElc significantly suppressed accumulation of MCMV tion by inducing changes to the host plant phenotype 
RNA. Conversely, MCMV accumulation was increased [53]. For example, cucumber mosaic virus (CMV) 2b 
on knocking down of ZmElc gene expression in maize protein promotes phloem ingestion of infected plants by 
[46]. This indicates that ZmELc has contrasting effects aphids [54]. Zucchini yellow mosaic virus (ZYMV) can 
on multiplication of SCMV and MCMV [47]. Though induce changes in leaf color and volatile emissions to 
the MCMV titer is generally increased under double attract more aphids to the infected plant. The recruitment 
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 6 of 21
of more aphids not only helps to spread ZYMV faster but [59]. The N-terminal region of the MCMV CP is rich in 
it can also give a free ride to the co-infecting Watermelon basic amino acids. A confocal microscopic analysis has 
mosaic virus (WMV) [55]. In fact, the HC-Pro of one pot- indicated that these basic residues are essential for the 
yvirus may interact with the CP of another potyvirus and nuclear localization of the CP [60]. Further, it was shown 
could promote the transmission of the latter [56]. Though that the MCMV CP interacts with importin-α and its 
both ZYMV and WMV are potyviruses, it is not clear nuclear import is most likely mediated by the importin-
whether any of the maize infecting potyviruses can lead α/β pathway [60]. Therefore, it will be useful to investi-
to increased recruitment of vectors. On the other hand, gate whether there is any allelic difference between the 
MCMV infection leads to strong induction of three vola- importins of resistant and susceptible cultivars.
tile compounds in maize seedlings that can attract both Mutagenesis analysis has shown that MCMV coat pro-
sexes of maize thrips (F. williamsi) and male onion thrips tein as well as two movement proteins (P7a and P7b) are 
(T. tabaci), which are important vectors for MCMV required for cell-to-cell movement in maize [61]. The 
[57]. It is unknown whether recruitment of multiple P31 protein, which is a readthrough extension of P7a, 
MLN-causing viruses to the same vector occurs. How- is required for efficient systemic infection [61]. The P31 
ever, combinations of up to four viruses: MCMV, SCMV, protein of beet necrotic yellow vein virus (BNYVV) has 
MSV and Maize yellow dwarf virus-RMV (MYDV-RMV) been shown to up-regulate pathogenesis-related (PR) 
have been found in both symptomatic and asymptomatic protein 10 in Nicotiana benthamiana [62]. The BNYVV 
maize plants that might have been transferred by one or P31 is also involved in efficient vector transmission, 
more vectors [23]. Better understanding of co-existence and induction of severe symptoms in some plants [63]. 
mechanisms of multiple viruses and virus-virus inter- MCMV P31 plays an important role in viral accumula-
actions might enhance breeding efforts for developing tion and symptom development by reducing the expres-
durable-resistant germplasm. sion of salicylic acid (SA)-responsive PR genes in maize 
[64]. It can also bind to and enhance enzyme activity 
Genome overview of viruses associated with maize lethal ZmPAO1 (polyamine oxidase 1) to counteract Zma-
necrosis miR167-mediated defense response of the host plant 
The MCMV virus genome comprises of a 4.4  kb sin- [65]. Another unique protein, P32, encoded in the 5’ end 
gle-stranded positive-sense ( +) RNA genome that of the viral genome, is required for increased accumula-
potentially encodes 7 proteins (Fig.  3). MCMV pro- tion of viral particles and severity of viral symptoms in 
duces 2 sub-genomic RNAs: RNA 1 (1.47 kb) and RNA maize plants [61].
2 (0.34  kb) [58]. The sub-genomic RNA1 encodes four The MCMV RNA also contains a cap-independent 
proteins P7a, P31, P7b and coat protein (CP) (Fig.  3) translation element (CITE) in its 3’-untranslated region 
Fig. 3 Genome map of MCMV and SCMV. A) The genome map of MCMV genomic RNA, isolate KS1 (NCBI Accession # NC_003627), B) The genome 
map of SCMV isolate SCMV Manyara08-TZA, complete genome (NCBI Accession # MN813967)
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 7 of 21
(UTR). Eukaryotic translation initiation factor 4E (eIF4E) [76]. While interaction of VPg with eIF4E can promote 
binds to  MCMV CITE (MTE) despite the absence of a viral RNA translation, its interaction with ZmElc may 
m7GpppN cap structure, which is generally required also promote viral replication [46]. The central domain 
for eIF4E to bind to P32 RNA [66]. Therefore, eIF4E has of VPg also interacts with the multifunctional viral pro-
been predicted as a soft target for engineering MCMV tein HC-Pro [81]. The variant of VPg protein of Tobacco 
resistance [67]. Disruption of the function of the reces- Etch Virus (TEV) determines the wilting and non-wilt-
sive eIF4E gene has resulted in resistance to potyviruses ing symptoms [82]. Human astrovirus VPg, which has 
ZYMV and papaya ring spot mosaic virus-W as well as sequence similarity to potyviral VPg is essential for 
cucumber vein yellowing virus in cucumber [68]. Though virus infectivity [83]. The VPg domain of TEV interacts 
no report has been made on eIF4E as a susceptibility fac- with host components to facilitate long-distance move-
tor for MLN disease, it will be worthwhile to determine ment and systemic infection [77]. Proteomic analysis 
whether allelic differences exist between susceptible and of Arabidopsis thaliana plants infected with TEV indi-
resistant cultivars of maize. cated that VPg also interacts with G-box regulating fac-
Though heat stress is generally thought to suppress the tor 6 and mitochondrial ATP synthase δ subunit [84]. 
plant immunity, plants use heat shock proteins (HSPs) as Besides VPg interacts with eIF4E(iso), eIF4F and eIF4G 
common mediators for both biotic and abiotic stresses [85]. Therefore, VPg is crucial for potyviral infection, 
[69]. HSPs modulate the plant immunity by changing the and a detailed study is required to identify all its tar-
level of accumulation and stability of PR-proteins [70]. gets in maize. It will be useful to know whether MCMV 
HSP24 is involved in the resistance to a fungal pathogen CITE (MTE) and potyviral VPg act synergistically or 
in postharvest grapes [71]. Tomato yellow leaf curl virus compete to promote viral replication, and if the latter, 
(TYLCV) CP interaction with the HSP70 is required for which has higher affinity to eukaryotic translation ini-
viral infection [72]. Since maize HSP70 also gets upreg- tiation factors (eIF).
ulated during MCMV infection [44], it will be useful to In general, the movement proteins are clustered at the 
verify if MCMV CP interacts with maize HSP70 and if 5’-end while the proteins related to the viral replication 
the later regulates the MCMV infection. are skewed towards the 3’-end of the potyvirus RNA 
The MLN-causing potyviruses have a single-stranded genome. A trypsin-like serine proteinase (P1) improves 
positive-sense ~ 10  kb RNA genome (Fig.  3). Sequence viral replication and cell-to-cell movement but is not 
similarity among SCMV isolates from different parts required strictly for viral infectivity [86]. The helper 
of the world ranges from 79 to 90% [73]. The potyvi- component proteinase (HC-Pro), located right to P1, is 
ral genome contains fixed hypervariable areas that are a multitasking protein that acts as a regulator of trans-
involved in wide-range of host adaptation [74]. Metagen- mission specificity by helping the virus to be held in the 
omic analysis indicated that the SCMV population in aphid stylets [87]. It also acts as a suppressor of host-
Kenya is highly diverse and can be divided into three plant resistance by suppressing post-transcriptional gene 
genetically distinct groups [23]. Moreover, the potyvi- silencing (PTGS) [86, 88–90]. The central region of HC-
ruses of Kenya are genetically different from isolates from Pro is important for the synergistic infection by PVX and 
other parts of the world. PVY; however, WSMV lacking HC-Pro is competent to 
The potyviral genome contains a single long open produce disease synergism in co-infections with MCMV 
reading frame (ORF) that is co- and/or post-transla- [21]. Maize plants infected with either MCMV or WSMV 
tionally cleaved to give rise to different viral proteins. It failed to show systemic infection while plants double 
is polyadenylated at its 3’-end and carries a viral protein infected with both MCMV and WSMV (with or without 
genome-linked (VPg) domain at the 5’-end instead of HC-Pro) showed systemic infection. This indicates that a 
the 5’- cap structure. The VPg is essential for viral rep- factor present in MCMV might have promoted WSMV 
lication [75], translation [76] and movement [77]. The multiplication while one or more WSMV factor other 
interaction between VPg and eIF4E is crucial for suc- than HC-Pro led to systemic movement and infection 
cessful viral infection [78, 79] and variations in the VPg by both viruses. Moreover, high-throughput sequenc-
central domain are associated with resistance-break- ing has shown that the HC-Pro coding region of SCMV 
ing in tobacco plants [80]. The m7G cap is required increases levels of SCMV-derived vsiRNAs in SCMV and 
for RNAs to bind to  the eIF4E and associate with the SCMV + MCMV inoculated maize plants [51]. The P3 
translation machinery. The VPg directly binds the cap- protein of potyviruses has been linked to symptom devel-
binding site of eIF4E and inhibits eIF4E-dependent opment, while the cytoplasmic inclusion (CI) protein is 
host RNA export and translation in human cells [78]. involved in RNA replication and cell-to-cell movement 
Therefore, VPg can direct preferential translation of by forming a tunnel through the plasmodesmata [86, 91]. 
viral genome while suppressing host mRNA translation The coat protein participates in cell-to-cell and systemic 
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 8 of 21
movement in coordination with movement proteins and chr. 3, respectively (Fig. 4, Table 1) [97, 98]. A maize 
(MPs). m-type thioredoxin gene ZmTrm2 on chr. 5 also inhib-
its SCMV and another potyvirus, tobacco vein-banding 
Genetic architecture of MLN‑associated virus resistance mosaic virus (TVBMV) [99]. The Wsm1 gene on chr. 6 
in maize—knowledge from identified QTLs and genes provides resistance to WSMV, MDMV and SCMV [93]. 
Host plant resistance mechanisms for MLN can be Another two genes, Wsm2 and Wsm3, provide resist-
divided into two types: 1) single R-gene mediated resist- ance to WSMV. Though these two genes do not provide 
ance that is race-specific and 2) broad-spectrum resist- protection against MDMV, they function synergistically 
ance acquired due to mutation in susceptibility genes with Wsm1 to increase resistance against MDMV. All 
or host-factors that would otherwise support the viral three genes showed equal resistance against SCMV in 
invasion, systemic movement and/or viral replication. the field. Redinbaugh et al. [92] have shown that Mdm1, 
Though only a few R-genes conferring resistance to dif- Scmv1, and Wsm1 map to same chromosomal location, 
ferent potyviruses have been reported, several QTLs have while scmv2 and Wsm2 are co-located at another fixed 
been discovered showing resistance to either or both locus (Fig. 4). Zambrano et. al [96] identified two QTLs 
principal MLN causing viruses. on chr. 3 and 10 of maize inbred line Oh1VI that might 
A few maize inbred lines showing resistance to differ- contribute to MLN resistance by conferring tolerance to 
ent potyviruses involved in MLN have been identified. different potyviruses.
Resistant inbred lines do not contain detectable viral Similarly, several maize inbred lines have been identi-
titers in systemically infected leaves [92–95]. Genetic fied with tolerance to MLN [107]. Four maize inbred 
studies indicate that one- or two-gene models can lines (KS23-6, N211, DR, and Oh1VI) have been identi-
explain the SCMV and MDMV resistance, while a fied that develop fewer symptoms for both MCMV and 
three gene model is required to explain WSMV resist- MLN than susceptible controls, while having virus titers 
ance [96]. Two major genes controlling SCMV resist- similar to those of susceptible plants [94]. This indicates 
ance (scmv1 and scmv2) have been identified on chr. 6 that these plants are not resistant to virus multiplication 
Fig. 4 Genetic map of MLN resistance. Different QTLs with high phenotypic variance and putative genes linked to resistance to MLN or MLN 
causing viruses are presented. The chromosomal locations are estimated based on B73 genome V4, and may not thus represent exact location
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 9 of 21
Table 1 Genes and QTLs for MLN resistance
Sl. No QTL name Author’s Source of Viral Chr Position/ location LOD Score R2*100/PVE % Reference
nomenclature favorable resistance of closest 
Allele marker(s)
1 qMCMV6-155.6 - KS23-6 MCMV Resist- 6 S6_155,627,528 42.30 98.00 [94]
ance
2 qMCMV6-156.5 - KS23-5 MCMV Resist- 6 S6_156,591,426 39.80 94.00 [94]
ance
3 qMCMV10- - DR MCMV Resist- 10 S10_135,801,262 8.90 31.00 [94]
135.8 ance
4 qMCMV5-4.3 - N211 MCMV Resist- 5 S5_4,322,924 9.60 38.00 [94]
ance
5 qMCMV2-163.8 - Oh28 MCMV Resist- 2 S2_163,825,081 10.3 18.00 [94]
ance
6 qMCMV3-137.2 - Oh1VI MCMV Resist- 3 S3_137,246,834 4.3 16.00 [94]
ance
7 qMCMV10- - Oh1VI MCMV Resist- 10 S10_134,058,628 8.7 11.0 [94]
134.0 ance
8 qMLN3-108.7 qMCMV3-108/ CML 550 MCMV and 3 108,706,910 25.34 23.73 [100]
qMLN3-108 MLN resistance
9 qMLN6-17.1 qMCMV6-17/ CML 550 MCMV and 6 17,165,743a - 22.90 [100]
qMLN6-17 MLN Resist-
ance
10 qMLN3-119.6 qMLN3-119 CML 550 MCMV and 3 119,614,021a - 10.90 [100]
MLN Resist-
ance
11 qMLN3-125.0 qMLN3_130 CKDHL0221 MCMV + SCMV 3 125,077,922– 24.64 26.00 [101]
Resistance 169,771,952
12 qMLN3-52.8 qMLN3_142 CKDHL0221 MCMV + SCMV 3 52,804,070– 13.19 12.71 [101]
Resistance 142,821,031
13 qMLN3-68.5 qMLN3_142 CML543 MCMV + SCMV 3 68,596,995– 17.68 11.09 [101]
Resistance 146,966,676
14 qMLN3-133.0 qMLN3_142 CKDHL0089 MCMV + SCMV 3 133,048,570– 50.02 27.46 [101]
Resistance 142,821,031
15 qMLN5-23.1 qMLN5_190 CML494 MCMV + SCMV 5 23,135,578– 5.14 15.91 [101]
Resistance 191,075,472
16 qMLN5-200.9 qMLN5_202 CML494 MCMV + SCMV 5 200,938,637– 7.62 16.65 [101]
Resistance 204,993,639
17 qMLN6-84.6 qMLN6_85 CML 494 MCMV + SCMV 6 84,664,840– 17.96 21.64 [101]
Resistance 91,883,155
18 qMLN6-156.3 qMLN6_157 CKDHL0089 MCMV + SCMV 6 156,386,857– 3.20 14.95 [101]
Resistance 157,568,432
19 qMLN9-132.7 qMLN9_142 CML543 MCMV + SCMV 9 132,762,904– 34.18 10.54 [101]
Resistance 147,131,097
20 qSCMV3-57.0 - Oh1V1 SCMV resist- 3 57,089,633– 10.40 13.00 [96]
ance 158,513,757
21 qSCMV6-9.4 - Oh1V1 SCMV resist- 6 9,498,343– 13.60 18.00 [96]
ance 31,412,155
22 qWSMV6-9.4 - Oh1V1 WSMV resist- 6 9,498,343– 8.30 12.00 [96]
ance 31,412,155
23 qMLN3-125.1 qMLN_03-130 CML543 MLN resistance 3 125,192,432– 27.48 37.80 [102]
130,082,791
24 qMLN3-146.2 qMLN_03-146 CML543 MLN resistance 3 146,251,234– 30.07 43.84 [102]
146,250,249
25 qMLN1-237.4 qMLN_01-241 CML543 MLN resistance 1 237,487,786– 7.02 10.46 [102]
241,184,216
26 qMLN5-190.6 qMLN_05-190 CML444 MLN resistance 5 190,677,275– 9.55 10.44 [102]
191,075,557
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 10 of 21
Table 1 (continued)
Sl. No QTL name Author’s Source of Viral Chr Position/ location LOD Score R2*100/PVE % Reference
nomenclature favorable resistance of closest 
Allele marker(s)
27 qMLN5-199.4 qMLN_05-199 CML543 MLN resistance 5 199,499,548– 15.36 17.74 [102]
199,499,538
28 qMLN6-85.2 qMLN_06-85 CML543 MLN resistance 6 85,203,511– 10.32 10.90 [102]
85,206,463
29 qMLN3-122.4 qMLN_03-126 CML444 MLN resistance 3 122,493,752– 6.32 10.55 [102]
126,171,099
30 qMLN6-5.1 qMLN_06-06 CML539 MLN resistance 6 5,159,730 8.15 14.15 [102]
6,270,908
31 qMLN3-129.0 qMLN_03-130 CML144 MLN resistance 3 129,095,914 5.60 16.63 [102]
131,969,810
32 qMLN9-95.7 qMLN_09-100 Mo37 MLN resistance 9 95,769,540– 5.33 16.32 [102]
113,201,792
33 qMLN3-113.8 qMLN_03-129 CML144 MLN resistance 3 113,820,730 5.58 13.97 [102]
129,095,914
34 qMLN8-156.3 qMLN_08-157 Mo37 MLN resistance 8 156,320,002 4.32 13.94 [102]
157,402,090
35 - scmv1/ZmTrxh/ Pa405 SCMV resist- 6 24,034,207– - - [98, 103, 104]
Zm00001d035390/ ance 24,035,363
wsm1/Mdm1
36 - scmv2/ Pa405 SCMV resist- 3 134,550,012– - - [97, 104]
Zm00001d041711/ ance 34,554,530
wsm2
37 - wsm3 Pa405 SCMV resist- 10 umc163 - - [104]
ance
38 - ZmTrm2 SCMV/MDMV/ 5 193,879,362– - - [99]
WSMV resist- 193,879,998
ance
39 - GRMZM2G134857 MLN resistance 4 S4_199711804 - 12 [105]
40 - GRMZM2G024159 MLN resistance 1 S1_44539940 1 - 10 [105]
41 qMLN6-155.4 qMLN06.157 KS23-5 MLN resistance S6_155,436,477— 20.93 60.62 [106]
S6_161,415,596
Since some of the QTLs had confusing nomenclature or no nomenclature assigned by authors, we generated a unique name for each QTL. In our nomenclature, 
the QTL starts with a code ‘q’ followed by a short code for the resistance trait. The next one or two digits before the hyphen represent the chromosome number. 
The numbers after the hyphen represent the chromosomal location (in Mb) of the starting coordinates of the QTL in MB with one decimal point. We have used the 
first decimal point without rounding the number so that it can look closer to the original QTL location. Our nomenclature is given in column 2. We have given QTL 
interval for most of the QTLs. Wherever the QTL interval is not available only marker position is given. AUDPC (Area under disease progression curve) values have been 
preferred over DS (disease severity) values wherever available
Chr Chromosome number, LOD Score Logarithm of the odds, R2/PVE Phenotypic variance explained in percentage. ‘-’: Data not available
a The QTL position is based on trait-associated markers of the joint linkage association mapping based on combined three double haploid populations
though they do not exhibit the disease symptom. One MCMV tolerance indicating a difference in the genetic 
or more host plant susceptibility factors promote the composition between both genomic loci, or an epistatic 
MCMV/MLN symptoms in susceptible plants rather interaction with a different genomic locus. Though the 
than the viral genes on their own. Absence of these sus- smaller population size might have overestimated effects, 
ceptibility factors or presence of alternate or mutant these QTLs can be useful for breeding MLN tolerant 
alleles lead to tolerant phenotype. Two QTLs have been lines and combining them can result in highly tolerant 
identified on chr. 3 and 5 of N211, which explain more hybrids. Identification of candidate gene(s) underpinning 
than 37% of the phenotypic variance [94]. Another the function these QTLs can be helpful for crop improve-
unique QTL was discovered on chr. 6 of KS23-6, which ment via precision genetic technology. A different QTL 
alone explained nearly all of the phenotypic variance for was discovered on chr. 10 in a population derived from 
MCMV tolerance (Fig.  4, Table  1) [94]. A similar QTL, inbred line DR that could explain 35% of phenotypic vari-
discovered in the corresponding chromosomal region ance [94]. Four other QTLs were discovered on chr. 1, 2, 
of KS23-5, explains slightly less phenotypic variance for 3 and 10 of Oh1VI, which altogether explained more than 
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 11 of 21
56% of phenotypic variance for MCMV resistance [94]. was upregulation was observed in miR159 expression-
Two major effect QTLs, qMCMV3-108/qMLN3-108 inhibited Arabidopsis or rice lines [110]. This indicates 
and qMCMV6-17/qMLN6-17 were identified on chr. 3 that there is a difference in miR159 mediated defense 
and 6 by linkage mapping and genome-wide association response between different species. The miR159 also 
studies (GWAS) conducted on three doubled-haploid regulates the vegetative growth and the timing of the 
populations and 380 diverse IMAS (improved maize for juvenile-to-adult transition by repressing GAMYB and 
African soil) maize lines [100]. Each of these QTLs con- GAMYB-like transcription factors [111, 112]. Similarly, 
fer tolerance to both MCMV and MLN across genetic miR159 controls the floral organ development in coor-
backgrounds and environments. Awata et al. [101] identi- dination with miR319 [113]. Therefore, downregula-
fied seven other QTLs for tolerance to MLN infections, tion of miR159 may negatively affect the vegetative and 
which are stable across different genetic backgrounds and floral development in maize plants. In Arabidopsis, 
environments. miR159 is upregulated in response to ABA and drought; 
Most of the MLN tolerance QTLs are concentrated and silences several MYB transcription factors that are 
around the centromeric regions of chr. 3 or chr. 6 (Fig. 4). known to positively regulate ABA responses. This con-
Multiple QTLs effecting large phenotypic variance for trasting role of miR159 has been predicted to desensitize 
MLN symptoms are located on ends of chr. 6 (Table  1) the effects of ABA and related stresses and allow plants 
and should be prioritized for additional study to iden- to grow normally [114]. Under drought stress, miR159 
tify the candidate genes and/or regulatory elements that also gets upregulated in subtropical maize drought-tol-
underpin the QTL functions. Identification of QTLs at erant genotype HKI-1532 in comparison to the suscep-
different chromosomal loci indicate that MCMV toler- tible V-372 line [115]. Similarly, miR159 expression is 
ance is controlled by multiple genetic elements [102] and significantly upregulated in the leaves of drought tolerant 
pyramiding of these elements may provide high-level wheat lines under drought stress [116]. This suggests that 
resistance/tolerance. However, many of these QTLs rep- the downregulation of miR159 in MLN infected plants 
resent large chromosomal segments that may include may challenge these plants to quickly neutralize the effect 
multiple genes and regulating elements. Therefore, can- of drought.
didate gene identification will require fine mapping and The Arabidopsis miR393 contributes to antibacterial 
functional validation, with priority placed on regions resistance by repressing auxin signaling [117]. On the 
where estimated effect size is large and where recombi- other hand, downregulation of miR393 enhanced drought 
nation is more frequent (marker assisted selection within tolerance by decreasing stomatal density and alleviat-
regions with higher rates of LD decay will be less effective ing leaf chlorosis in barley [118]. In Arabidopsis, miR393 
than in low recombination centromeric blocks). expression is strongly upregulated by dehydration, cold, 
NaCl and ABA treatments [119]. However, miR393 was 
Role of miRNA in MLN disease significantly upregulated in response to drought stress in 
The microRNAs (miRNAs) are conserved, non-coding, both tolerant maize inbred line HKI-1532 and suscepti-
small RNA molecules of 20–22 nucleotides, which are ble line V-372 [115]. This indicates that the downregula-
known to play important roles in host plant resistance to tion of miR393 by double infection of SCMV and MCMV 
viruses. Analysis of miRNA profiles, therefore, can help may not have much impact to drought tolerance of the 
to decipher the response of the host plants to viral infec- plant while it may compromise the disease resistance.
tion. An expression profile of maize miRNAs, obtained Overexpression of soybean miR394 in Arabidopsis 
by challenging maize inbred line B73 with MCMV and leaf lowered water loss and enhanced drought tolerance 
SCMV individually and in combination revealed that [120]. Similarly, miR394 was also upregulated in drought 
expression patterns of most miRNAs were similar for sin- tolerant mung bean leaves [121]. However, miR159 and 
gle infection of SCMV and double infection with SCMV miR394 were down-regulated in either MCMV only or 
and MCMV except three miRNAs (miR159, miR393, SCMV and MCMV coinfected maize leaves [108]. This 
and miR394) that were downregulated by the synergis- indicates that the MLN infected maize lines may show 
tic infection of both viruses [108]. In silico analysis indi- lower drought tolerance, which is important for the sub-
cates that these miRNAs could be playing a role in the Saharan Africa.
MCMV and SCMV interaction [39]. Besides viral resist- The expression of miR167 gets upregulated upon 
ance, these miRNAs have been speculated to have roles MCMV infection in resistant maize lines [65]. It plays 
in drought tolerance [109].   a key role in antiviral resistance during single infec-
The downregulation of miRNA159 upregulates genes tion by MCMV only or even during double infection by 
associated with defense and programmed cell death MCMV and SCMV by targeting Auxin Response Fac-
such as PR genes in Tobacco though no such PR gene tor3 (ZmARF3) and ZmARF30 in maize. In contrast, 
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 12 of 21
miR167 gets down-regulated under drought stress in Factors that may influence future MLN threat 
maize seedlings [122]. It has been predicted that down- to maize
regulation of miR167 might result in accumulation of Influence of likely climate changes
its target Phospholipase D mRNAs to initiate the regu- A rise in the average global temperature by 2.0–4.9 °C 
lation of ABA-induced stomatal movement and antioxi- is likely by the end of this century [125], leading to 
dant defense. expanded ranges and severities of many pests and 
RNA silencing provides immunity in most eukaryotes pathogens [126, 127]. Although MLN is caused by 
against invading viruses. DICER-like (DCL) proteins co-infection of MCMV and potyvirus, infection by 
play an important role in RNA silencing by recogniz- MCMV alone can also result in MLN like symptoms if 
ing and cleaving double-stranded RNA (dsRNA) from occurring under abiotic stress [6]. MCMV infection in 
replication intermediates as well as highly structured maize increases the abundance of HSP70 [44], which 
single-stranded RNA (ssRNA) of viruses to gener- is involved in enhancing drought and heat stress tol-
ate small interfering RNAs (siRNAs), which, in turn, erance [128–130]. HSP70 has been linked to increased 
triggers specific virus clearance process in the RNA- TYLCV multiplication in tomato [72], and to virus 
induced silencing complex (RISC) by an Argonaute susceptibility in Arabidopsis [131, 132] and rice [133]. 
(AGO) protein [123, 124]. The DCL4 and DCL2 play The HSP70  gene is transcriptionally up-regulated due 
an vital role in defense against certain ( +)-strand RNA to drought and heat stress in rice (O. sativa) and maize 
viruses in a hierarchical and redundant manner [51]. [134, 135]. Though HSP70 helps in drought and heat 
The expression of DCL2 increased when plants were tolerance, HSP70 and 90 are the most frequent chap-
infected with either of the two viruses and its expres- erons utilized by viruses [136]. Because HSP70 plays 
sion increased significantly during coinfection with contrasting roles in abiotic stress tolerance and virus 
SCMV and MCMV leading to a synergistic plant reac- susceptibility, it is important to dissect the HSP70 bio-
tion in susceptible maize line B73 while the expression chemical pathway to identify unique factor(s) that help 
level of DCL4 was reduced [51]. In absence of DCL4, in MLN susceptibility but not heat and drought toler-
DCL2 generates 22 nt surrogate viral small interfer- ance, which are critical objectives of maize breeding 
ing RNAs (vsiRNAs), which are less efficient in antivi- for sub-Saharan Africa.
ral silencing and that may be the reason why B73 was Maize plants respond to increases in temperature 
still susceptible to SCMV and MCMV attack. Argo- during growth through increased respiration and faster 
naute (AGO) proteins, which form core components of completion of reproductive cycles. Temperatures above 
RNA-induced silencing complexes (RISCs), are another 32 °C during and after flowering can induce tassel blast-
important class of molecule involved in RNA silencing. ing, pollen sterility, plant barrenness, kernel abortion 
Two AGOs (2a and 18a) were significantly up-regulated or shriveled grain leading to reduced grain yield [137–
by double infection with SCMV and MCMV. Probably 141]. Farmers experiencing increased incidence of 
they had least impact on limiting MLN viruses [51]. A heat-stress related productivity losses may alter plant-
further comparison of expression of AGOs in suscep- ing dates, irrigation frequency, cultivar use and plant-
tible and resistant cultivars is required to understand, ing locations potentially extending the green bridge and 
which AGOs play vital role in gaining MLN resistance. enabling more virus transmission [127].
Viral small interfering RNAs (vsiRNAs) can also target Higher temperatures potentially favor both the 
host genes to mediate disease symptoms in plants [52]. insect-transmitted MLN viruses and insect vector 
Both SCMV and MCMV have plethora of vsiRNAs dis- populations [142, 143]. Elevated temperatures may 
tributed throughout their genomic RNAs, which were negatively affect the plant responses to viral attack, 
predicted to target genes involved in metabolic path- especially RNA silencing, vector attractiveness, and 
ways, biosynthesis of secondary metabolites, transcrip- insect probing time. It may also cause shifts in natural 
tion regulation and protein phosphorylation [51]. Double enemies of viral vectors, increasing transmission rates 
infection of MCMV + SCMV, resulted in higher accumu- and frequency of MLN outbreaks [143–145]. Addi-
lation of MCMV vsiRNA than single infection in maize tional challenges may result from shifts in pest dynam-
(Zea mays L.) inbred line B73, which is consistent with ics. Increased temperatures in the savannah may also 
double infection being more damaging than infection by worsen maize infestation by parasitic weeds of the 
either of the viruses alone. The siRNA expression profile Striga genus [146]. Viruses and parasitic plants share 
of MLN infected leaves indicated that the viral capsid some resistance response pathways in plants including 
proteins, P7a and P7b were the most expressed genes fol- maize [38, 147–149]. Therefore, coinfection of viruses 
lowed by the replicase, while P32 domain showed moder- and Striga spp. might overwhelm the plant resistance 
ate expression in the plant [39]. mechanisms and exacerbate yield losses. Therefore, 
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 13 of 21
Table 2 Country specific demographic information on the role of maize in food security
Country Population Projected Poverty (%)a Total domestic Total domestic Total domestic Maize Calorie intake Calorie intake Projected Projected 
(million)a population maize supply maize supply maize supply consumption (kcal/daily/ from maize consumption consumption 
(2050)b (MMT) (%) for food (%) for feed (yearly/kg/ capita)c and (% share)c in 2030 in 2050 (yearly/
capita)c (yearly/kg/ kg/capita)d
capita)d
Ethiopia 109.2 205.4 23.5 7.6 56 36 40.8 2285 386 (16.9) 47.1 55.5
Kenya 51.4 91.6 36.1 3.9 99  > 1 80.3 2139 709 (33.1) 66.5 54.4
Tanzania 56.3 129.4 26.4 5.5 62 22 64.5 2364 577 (24.4) 73 78.6
Uganda 42.7 89.4 21.4 2.6 74 15 49 2152 415 (19.3) 54.9 66
Sources: aWorld Bank [155]. Ethiopia and Kenya poverty level 2015, Uganda 2016 and Tanzania 2018, bWorld Bank [156]; cFAOSAT [157]; dAuthor’s calculation after estimating ARIMA model
Information on maize consumption and calorie intake are reported as triennium average (TE) ending 2017
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 14 of 21
development of MLN tolerant hybrids in the back- in all countries except Kenya. However, the population 
ground of heat and drought tolerant lines may ame- of Kenya is expected to double by 2050 (Table 2), which 
liorate the problem of small-holding maize farmers of will raise the total maize consumption by more than 25%. 
SSA. Therefore, it is imperative to supply more maize to ensure 
food security in these countries.
Influence of globalization and trade on spread of MLN Kenya is a net importer of maize. Uganda and Ethiopia 
Global trade-associated movement of plant materi- are net exporters, while Tanzania is nearly self-sufficient 
als across borders facilitates unwanted and probably [158]. The MLN outbreak led to a surge in maize import 
unnoticed transfer and spread of plant pathogens from by Kenya in 2011 (Fig. 5). As Kenya is a major importer 
endemic to non-endemic regions [126]. This may also of Ugandan maize, the export graph of Uganda reached 
lead to new host–pathogen, vector-pathogen or even its peak in 2012. Similarly, the maize import of Tanza-
host-vector-pathogen interactions. During 2000–2009, nia increased more than fivefold relative to the previous 
Kenya imported maize from at least 35 countries in the year after its maize harvest was devastated by MLN in 
world. MLN intrusion in Kenya may be linked to maize 2012 (Fig. 5). Tanzania spent US$ 24 million to support 
import from the international market, although such the extra maize import. The arrival of MLN to Ethio-
possibility is likely impossible to confirm or refute. pia in 2014 drastically affected its production leading to 
Human population has been predicted to increase by almost shutting down of maize exports (Fig.  5). Higher 
2.3 billion people by the year 2050 [150]. To meet the demand by Kenya and Tanzania to import, and less sup-
demand for maize by the increasing population in SSA, ply by Ethiopia created an imbalance in the maize supply 
governments may need to import maize grains even chain that led to increased producer price in Kenya and 
from MCMV endemic regions [151, 152], and some of Ethiopia.
this grain may be used as seed by farmers [153, 154]. Kenya imports maize mainly from Uganda, Zam-
This situation risks increasing the rate of introduction of bia, Tanzania and Mozambique [159], and is the sole 
different strains of MCMV, SCMV and other non-SSA- importer of Ethiopian maize [159]. In addition to Kenya, 
endemic potyviruses causing MLN outbreaks. Uganda exports maize to Rwanda, South Sudan, and 
Burundi. In the sampled countries, the poverty incidence, 
Current and future impacts of MLN in Africa measured by the headcount ratio at national poverty line, 
Although maize plays a significant role in the food secu- is widespread ranging from 21–36% [155]. Among the 
rity of many countries, we limit our discussion on the major maize importers from these four countries, 38% 
economic impacts of MLN to Kenya, Ethiopia, Tanzania of Rwanda’s population are below the national poverty 
and Uganda (Table 2). line, while approximately 65 and 82% are below the pov-
erty line in Burundi and South Sudan, respectively [155]. 
Impact of maize on food security and international trade Maize trade flows of the sampled countries warn that 
in SSA further maize production loss due to MLN or any other 
There is widespread heterogeneity in maize usage among causes, particularly in Uganda and Ethiopia, can have sig-
major MLN affected countries in SSA (Table  2). Our nificant negative impacts on the food security in Kenya, 
analysis indicates that Ethiopia utilized 56% of its domes- Rwanda, South Sudan and Burundi, who rely on maize 
tic maize supply as food, while almost all domestic maize from Uganda and Ethiopia.
was consumed as food in Kenya during 2015–2017. 
Uganda is the second highest consumer of maize (74%) as Quantification of economic impact of MLN outbreak in SSA
food, while in Tanzania 62% of maize supply contributed MLN began affecting Kenya and Ethiopia in 2011 and 
to food (Table 2). The contribution of maize to daily die- 2014, respectively. The reduction in maize yield led to 
tary energy in the sampled countries is also heterogene- shortages that were reflected in increased producer price 
ous, ranging between 17 and 33% (Table 2). Irrespective of maize in Kenya by ~ 30% in 2011 [160]. Similarly, the 
of the variability in the relative importance and the uses producer price of maize in Ethiopia increased by ~ US$ 
of maize in these countries, the outbreak of MLN created 16/ton in 2014 [160]. The MLN-induced maize price 
havoc on the economy and food security of all. The popu- hikes also affected per capita maize consumption in these 
lation of these countries may grow between 78 to 129%, countries. Figure 6 shows that the yearly per capita maize 
thereby doubling to ~ 516 million by 2050 (Table 2). We consumption reached the minimum in 2012 and 2015 in 
estimated the per capita maize consumption in 2050 by Kenya and Ethiopia, respectively, compared with the pre-
applying the autoregressive integrated moving average vious years. The import price of maize in Rwanda also 
(ARIMA) model for this region. Our estimation indi- increased by 65.8% (to USD 252/ton) in 2014 compared 
cates that per capita maize consumption will increase to 2012 due to elevated maize demand [159]. MLN thus 
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 15 of 21
Fig. 5 Impacts of MLN on maize imports of Kenya and Tanzania as well as exports from Ethiopia and Uganda. Source: [158]. Note: First report of 
MLN in Kenya was in 2011, in Ethiopia 2014; Uganda and Tanzania, 2012
Fig. 6 Maize consumption trends of Kenya, Ethiopia, Uganda and Tanzania (Kg/per capita/year). Source: Authors based on FAOSTAT [158]
generated havoc on the already precarious food secu- Prospects of genetic engineering and genome 
rity situation in the sampled countries and their trading editing in development of MLN resistant 
partners. germplasm
As seen with other disease outbreaks, integrated 
Biswal et al. BMC Plant Biology          (2022) 22:542 Page 16 of 21
management approaches enhance the overall response and minor QTLs can be targeted to pyramid high-level of 
to disease outbreaks and often lead to effective lifespan resistance to MLN [170].
of each component. Early detection of MLN pathogens The US Department of Agriculture (USDA) has 
is the primary requirement for managing the disease at declared that it would not regulate plants that could oth-
the national and international levels. Sensitive diagnos- erwise have been developed by conventional breeding 
tic tools have already been developed based upon sero- techniques as long as they are not plant pests or devel-
logical and molecular tools for early detection of MLN oped using plant pests [166, 171]. Since a few naturally 
pathogens and their management. The monitoring and resistant maize germplasms have already been identified 
control of cross-border transmission of MLN viruses and such resistant allele genes can be transferred to elite 
has partly been addressed through an MLN phytosani- lines by traditional breeding, modification of their alter-
tary community of practice that enforces appropriate native alleles to resistant version or even pyramiding of 
phytosanitary measures [11]. Other MLN management multiple such resistant loci by genome editing may not 
strategies include use of MLN tolerant and virus-free attract regulation from USDA. Similarly, plants with 
seeds, vector control, rotation and rogueing [161]. directed mutation in the target gene won’t be treated 
However, the economic status of the farmer and access as transgenic (genetically modified organism, GMO) in 
to technologies remain the major influencer of the Japan [172]. Recently, Government of India decided that 
MLN management approaches to be adopted. Among genome edited products, free from exogenous DNA and 
all proposed or implemented MLN management strate- falling under SDN1 or SDN2, will be exempted from 
gies, development of MLN resistant germplasm is the biosafety assessment [173]. The China’s Ministry of Agri-
most effective, durable and economically viable control culture and Rural Affairs has issued a guideline according 
measure. to which gene-edited crop varieties will need less com-
Expression of viral coat protein in host plants has been plicated food and environmental safety evaluations com-
demonstrated to provide resistance against target viruses pared to true transgenics [174]. The developers need only 
[162], including to control MLN disease. Transgenic to provide laboratory data and conduct small-scale field 
maize plants expressing MDMV strain B capsid protein trials for approval by the regulatory bodies, which would 
did not show MLN symptoms when challenged with take significantly less time for release than regular trans-
MCMV and different strains of MDMV [163]. Though genic lines. The European Court of Justice, on the other 
this is a highly efficient approach for virus resistance, hand, has decided to regulate genome edited plants as 
transgenic crops are not currently accepted in many transgenic [175] whilst regulatory status for gene edited 
countries [164]. crops for most other countries, particularly Africa, is 
CRISPR-mediated genome editing has boosted our evolving.
ability to precisely target and modify sequences and 
expression of genetic elements. The CRISPR tools can Authors’ perspective
be safely and naturally segregated through independent In 2017, more than 820 million people in the world were 
assortment leading to plants, free of transgenic elements undernourished, of whom ~ 30% were concentrated in 
[165]. This may result in higher consumer acceptance Southern Africa [176]. More than 60% of this population 
with potentially fewer regulatory hurdles than transgenic suffers from moderate to extreme food insecurity. If the 
crops. Therefore, genome editing offers a novel oppor- current trends continue, the number of people in abject 
tunity to control viral diseases and may be exploited for poverty will increase further by 2050. It is imperative to 
development of MLN tolerant maize cultivars in coun- sustainably increase agricultural productivity to eliminate 
tries where cultivation of gene edited crops is permit- hunger. Notably, as maize supplies 25% of the per capita 
ted[166]. Additionally, gene editing offers a route to total daily dietary energy in Africa [5], sustainable maize 
broad functional validation of candidate genes poten- production is critical to food security in this region.
tially facilitating faster prioritization of targets to focus In general, maize yields in Africa lag far behind the 
on in conventional marker assisted breeding schemes for rest of the world. Various biotic stresses like MLN fur-
regions where cultivation of gene edited crops is not yet ther limit maize productivity. In 2014, about 60,000 ha 
permitted. of the Kenyan maize area were hit by MLN, causing 
Large effect QTLs (qMCMV6-155.6, qMCMV6-156.5 approximately US$ 50 million economic loss [177]. 
and qMCMV10-135.8) identified in KS23-5, KS23-6 and Since more than 70% of the farm households in Africa 
DR-derived populations are controlled by recessive genes are smallholders, development of stress-tolerant vari-
[94] that may be amenable to gene editing. With the eties and rapid scaling out of those technologies can 
recent additions of new tools like base editing [167] and contribute to food security and income for resource-
prime editing [168, 169], multiple genes from both major poor farmers. If we assume that 50% of the total 
B iswal et al. BMC Plant Biology          (2022) 22:542 Page 17 of 21
affected area can be planted with MLN tolerant/resist- reviewed the manuscript, edited several versions of the manuscript and vali-
ant maize, which can lower yield loss by 80%, the eco- dated the results. All authors read and approved the final manuscript.
nomic benefit can be as much as US $ 20 million every Funding
year in Kenya alone. The need to develop and dissemi- This study is supported by the CGIAR research program on MAIZE, and the 
nate MLN resistant maize cultivars in this region is project of Gene Editing to Control Maize Lethal Necrosis in Africa for Improved 
Grain Harvests funded by Bill and Melinda Gates Foundation (BMGF, No. 
apparent and imperative. R0208.02). The funders had no role in study design, data collection and analy-
Besides MLN, maize streak virus, parasitic weeds sis, decision to publish, or preparation of the manuscript.
(Striga hermonthica and Striga asiatica), ear rot fungi, 
Availability of data and materials
maize stem borers, fall armyworm, gray leaf spot, Not applicable.
Bipolaris maydis and downy mildew are economi-
cally important biotic constraints for maize produc- Declarations
tion in Africa [178, 179]. Abiotic constraints such as 
low soil fertility, drought and heat stress also cause Ethics approval and consent to participate
Not applicable.
significant yield losses [178, 179]. Therefore, MLN 
tolerant varieties must be resistant to multiple other Consent for publication
stresses. Genome editing shows promise for developing Not applicable.
MLN resistant varieties directly in elite African maize Competing interests
cultivars without affecting other stress tolerances, The authors declare that they have no competing interests.
agronomic performance, and consumer-preferred 
Author details
characteristics. Although it is beyond the scope of this 1 International Maize and Wheat Improvement Center (CIMMYT), Km. 45, 
review, it is important to implement policies, equitable Carretera Mexico-Veracruz, El Batan, Texcoco C.P. 56237, Mexico. 2 Stony Creek 
seed system models, and social communication strat- Colors, 921 Central Ave W, Springfield, TN 37172, USA. 3 Department of Biology, 
University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. 4 CIM-
egies to support the adoption of new technologies, MYT, Village Market, P. O. Box 1041, Nairobi 00621, Kenya. 
including improved varieties, which is complex and sel-
dom rapid [180]. Received: 27 June 2022   Accepted: 7 November 2022
Conclusion
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