2013
DOI: 10.1371/journal.ppat.1003465
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Myxoma Virus Protein M029 Is a Dual Function Immunomodulator that Inhibits PKR and Also Conscripts RHA/DHX9 to Promote Expanded Host Tropism and Viral Replication

Abstract: Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell line… Show more

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Cited by 58 publications
(95 citation statements)
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“…Like MPXV, MYXV pathogenesis is restricted to only certain species and has little or no capability for pathogenesis in all others (29,30). For both MYXV and MPXV, restriction in mice requires signaling through the type I and type II IFN pathways (20,30).…”
Section: Discussionmentioning
confidence: 99%
“…Like MPXV, MYXV pathogenesis is restricted to only certain species and has little or no capability for pathogenesis in all others (29,30). For both MYXV and MPXV, restriction in mice requires signaling through the type I and type II IFN pathways (20,30).…”
Section: Discussionmentioning
confidence: 99%
“…However, some sh20 was found in the nucleus, even though this form lacks this sequence, suggesting that OV20.0 has an additional mechanism for nuclear localization. This is reminiscent of myxoma virus M029, a functional ortholog of OV20.0 and E3, which like sh20 is missing around 80 amino acids from the N terminus (50). All poxviruses replicate and transcribe their genomes exclusively in the cytoplasm, which is then the main site of viral dsRNA production.…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, this mutated sequence has reverted to the original sequence twice on independent branches of the tree and in viruses isolated from widely separated geographic regions. M029 has been shown to function similarly to VACV E3, binding double-stranded RNA, inhibiting protein kinase R (PKR) activation, and inhibiting IFN-␤, tumor necrosis factor alpha (TNF-␣), and interleukin-6 (IL-6) expression (45); it is a critical virulence factor in rabbit infections but also has a second function of binding RNA helicase A (RHA; DHX9), which promotes virus replication in some cell lines, so it has been described as a dual-function virulence and host range factor (46). The amino acid sequence from the related leporipoxvirus RFV is conserved from amino acid 1 to 8 and is identical to that from MYXV from amino acid 20 to 55 but is poorly conserved between residues 9 and 19; this region is also divergent in the Californian MSW strain of MYXV (47).…”
Section: Pathways To Attenuation and Virulence In Australian Isolatesmentioning
confidence: 99%