Insights into the Functions of eIF4E-Binding Motif of VPg in Potato Virus A Infection

Saha, Shreya; Mäkinen, Kristiina

doi:10.3390/v12020197

Cited by 24 publications

(28 citation statements)

References 61 publications

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“…Potyviral protein VPg is responsible for this regulation. Our recent data suggest that binding of PVA VPg to eIF(iso) 4E is a key factor in directing PVA RNA from PGs to active translation on polysomes [ 45 ]. VPg also protects PGs from degradation via autophagy [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection

Pollari

Varjosalo

et al. 2020

PLoS Pathog

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In this study, we investigated the significance of a conserved five-amino acid motif 'AELPR' in the C-terminal region of helper component-proteinase (HCPro) for potato virus A (PVA; genus Potyvirus) infection. This motif is a putative interaction site for WD40 domain-containing proteins, including VARICOSE (VCS). We abolished the interaction site in HCPro by replacing glutamic acid (E) and arginine (R) with alanines (A) to generate HCPro WD. These mutations partially eliminated HCPro-VCS co-localization in cells. We have earlier described potyvirus-induced RNA granules (PGs) in which HCPro and VCS co-localize and proposed that they have a role in RNA silencing suppression. We now demonstrate that the ability of HCPro WD to induce PGs, introduce VCS into PGs, and suppress RNA silencing was impaired. Accordingly, PVA carrying HCPro WD (PVA WD) infected Nicotiana benthamiana less efficiently than wild-type PVA (PVA WT) and HCPro WD complemented the lack of HCPro in PVA gene expression only partially. HCPro was purified from PVA-infected leaves as part of high molecular weight (HMW) ribonucleoprotein (RNP) complexes. These complexes were more stable when associated with wild-type HCPro than with HCPro WD. Moreover, VCS and two viral components of the HMW-complexes, viral protein genome-linked and cylindrical inclusion protein were specifically decreased in HCPro WD-containing HMW-complexes. A VPg-mediated boost in translation of replication-deficient PVA (PVA ΔGDD) was observed only if viral RNA expressed wild-type HCPro. The role of VCS-VPg-HCPro coordination in PVA translation was further supported by results from VCS silencing and overexpression experiments and by significantly elevated PVA-derived Renilla luciferase vs PVA RNA ratio upon VPg-VCS co-expression. Finally, we found that PVA WD was unable to form virus particles or to spread systemically in the infected plant. We highlight the role of HCPro-VCS containing multiprotein assemblies associated with PVA RNA in protecting it from degradation, ensuring efficient translation, formation of stable virions and establishment of systemic infection.

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Section: Discussionmentioning

confidence: 99%

Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection

Pollari

Varjosalo

et al. 2020

PLoS Pathog

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“…Viruses of the family Potyviridae have a viral protein genome-linked (VPg) covalently attached at the 5' end of their RNA genomes instead of the 7-methylguanosine cap structure that is found at the 5' end of some eukaryotic and viral mRNAs. VPg has affinity to host eIF4E and its isoform not only for translation of viral proteins but also for viral RNA stabilization and evading antiviral RNA silencing ( Saha and Makinen, 2020 ); the degree of affinity is correlated with viral infectivity ( Leonard et al, 2000 ). Therefore, significant reduction of susceptibility to PVY N in tomato carrying 3DEL implies the possibility that the deletion mutation of 3DEL affects the affinity to PVY N VPg.…”

Section: Discussionmentioning

confidence: 99%

Artificially Edited Alleles of the Eukaryotic Translation Initiation Factor 4E1 Gene Differentially Reduce Susceptibility to Cucumber Mosaic Virus and Potato Virus Y in Tomato

et al. 2020

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Eukaryotic translation initiation factors, including eIF4E, are susceptibility factors for viral infection in host plants. Mutation and double-stranded RNA-mediated silencing of tomato eIF4E genes can confer resistance to viruses, particularly members of the Potyvirus genus. Here, we artificially mutated the eIF4E1 gene on chromosome 3 of a commercial cultivar of tomato (Solanum lycopersicum L.) by using CRISPR/Cas9. We obtained three alleles, comprising two deletions of three and nine nucleotides (3DEL and 9DEL) and a single nucleotide insertion (1INS), near regions that encode amino acid residues important for binding to the mRNA 5' cap structure and to eIF4G. Plants homozygous for these alleles were termed 3DEL, 9DEL, and 1INS plants, respectively. In accordance with previous studies, inoculation tests with potato virus Y (PVY; type member of the genus Potyvirus) yielded a significant reduction in susceptibility to the N strain (PVYN), but not to the ordinary strain (PVYO), in 1INS plants. 9DEL among three artificial alleles had a deleterious effect on infection by cucumber mosaic virus (CMV, type member of the genus Cucumovirus). When CMV was mechanically inoculated into tomato plants and viral coat accumulation was measured in the non-inoculated upper leaves, the level of viral coat protein was significantly lower in the 9DEL plants than in the parental cultivar. Tissue blotting of microperforated inoculated leaves of the 9DEL plants revealed significantly fewer infection foci compared with those of the parental cultivar, suggesting that 9DEL negatively affects the initial steps of infection with CMV in a mechanically inoculated leaf. In laboratory tests, viral aphid transmission from an infected susceptible plant to 9DEL plants was reduced compared with the parental control. Although many pathogen resistance genes have been discovered in tomato and its wild relatives, no CMV resistance genes have been used in practice. RNA silencing of eIF4E expression has previously been reported to not affect susceptibility to CMV in tomato. Our findings suggest that artificial gene editing can introduce additional resistance to that achieved with mutagenesis breeding, and that edited eIF4E alleles confer an alternative way to manage CMV in tomato fields.

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“…The intrinsic disorder that characterizes VPg protein [19][20][21] enables it to play multiple functions during viral infection [22][23][24]. VPg is involved in viral RNA translation probably both by recruiting host factors to promote translation initiation and by nucleating a protein complex around the viral RNA that protects it from the RNA silencing mechanism and facilitates its traffic to polysomes [25]. The interaction of VPg with the eukaryotic translation initiation factor eIF4E and/or its isoform eIFiso4E plays an important role in these functions.…”

Section: Introductionmentioning

confidence: 99%

Virus Host Jumping Can Be Boosted by Adaptation to a Bridge Plant Species

Martínez-Turiño

Calvo

Bedoya

et al. 2021

Preprint

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Understanding biological mechanisms that regulate emergence of viral diseases, in particular those events engaging cross-species pathogens spillover, are becoming increasingly important in Virology. Species barrier jumping has been extensively studied in animal viruses, and the critical role of a suitable intermediate host in animal viruses-generated human pandemics is highly topical. However, studies on host jumping involving plant viruses have been focused on shifting intra-species, leaving aside the putative role of “bridge hosts” in facilitating interspecies crossing. Here, we take advantage of several VPg mutants, derived from a chimeric construct of the potyvirus Plum pox virus (PPV), analysing its differential behaviour in three herbaceous species. Our results showed that two VPg mutations in a Nicotiana clevelandii-adapted virus, emerged during adaptation to the bridge-host Arabidopsis thaliana, drastically prompted partial adaptation to Chenopodium foetidum. Although, both changes are expected to facilitate productive interactions with eIF(iso)4E, polymorphims detected in PPV VPg and the three eIF(iso)4E studied, extrapolated to a recent VPg:eIF4E structural model, suggested that two adaptation ways can be operating. Remarkably, we found that VPg mutations driving host-range expansion in two non-related species, not only are not associated with cost trade-off constraints in the original host, but also improve fitness on it.

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Insights into the Functions of eIF4E-Binding Motif of VPg in Potato Virus A Infection

Cited by 24 publications

References 61 publications

Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection

Association of host protein VARICOSE with HCPro within a multiprotein complex is crucial for RNA silencing suppression, translation, encapsidation and systemic spread of potato virus A infection

Artificially Edited Alleles of the Eukaryotic Translation Initiation Factor 4E1 Gene Differentially Reduce Susceptibility to Cucumber Mosaic Virus and Potato Virus Y in Tomato

Virus Host Jumping Can Be Boosted by Adaptation to a Bridge Plant Species

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