Abstract
Myxoma virus (MYXV) is the prototypic member of the Leporipoxvirus genus of the Poxviridae family of viruses. In nature, MYXV is highly restricted to leporids and causes a lethal disease called myxomatosis only in European rabbits (Oryctologous cuniculus). However, MYXV has been shown to also productively infect various types of nonrabbit transformed and cancer cells in vitro and in vivo, whereas their normal somatic cell counterparts undergo abortive infections. This selective tropism of MYXV for cancer cells outside the rabbit host has facilitated its development as an oncolytic virus for the treatment of different types of cancers. Like other poxviruses, MYXV possesses a large dsDNA genome which encodes an array of dozens of immunomodulatory proteins that are important for host and cellular tropism and modulation of host antiviral innate immune responses, some of which are rabbit-specific and others can function in nonrabbit cells as well. This review summarizes the functions of one such MYXV host range protein, M029, an ortholog of the larger superfamily of poxvirus encoded E3-like dsRNA binding proteins. M029 has been identified as a multifunctional protein involved in MYXV cellular and host tropism, antiviral responses, and pathogenicity in rabbits.
Highlights
Myxoma virus (MYXV) is the prototypic member of the Leporipoxvirus genus of the Poxviridae family of viruses
Vaccines 2020, 8, 244 the ability of the virus to act as a highly transmissible host-restricted pathogen, MYXV was released in Australia and Europe to control the feral European rabbit populations [10]
Induction was compromised, possibly at the level of the initial sensing of the virus infection [87]. These findings were further confirmed by the observation that unlike primary mouse embryonic fibroblasts (pMEFs), the phosphorylation of ERK1/2 was not detectable, which was further confirmed that there was little or no induction of type I IFN production in the iMEFs [87]. These results indicated that pathogen-associated molecular patterns (PAMPs) sensing of MYXV in pMEFs is likely a key step in induction of type I IFN that is completely lost during the immortalization process
Summary
Myxoma virus (MYXV) is the prototypic member of the Leporipoxvirus genus of the Poxviridae family of viruses. The N-terminal domain might target more diverse species-specific antiviral pathways This domain-specific function was highlighted in multiple studies, where VACV E3L was replaced with other unrelated viral or even bacterial genes that encode proteins with a dsRNA-binding motif. HeLa cells; expression of the RNase II gene product of E. coli reversed this phenotype [36] Another example is influenza virus-encoded NS1 protein, which completely rescued VACV replication in cultured cells in the absence of E3L [37]. The orf virus-encoded E3 ortholog (OV20.0L gene), which shares only 31% amino acid identity to VACV E3 protein, can rescue. All the tested E3 orthologs had conserved dsRNA binding domains plus N-terminal Z-DNA binding domains (except M029) These results suggest that, highly conserved atx the amino acid level, the diverse poxvirus encoded dsRNA-BD might have adapted. Schematic of the E3-like protein domains encoded by vaccinia virus (VACV), monkeypox virus (MPXV) and myxoma virus (MYXV)
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