Myxoma virus

M-T7 Poxviruses Myxoma virus Resembles IFN7 receptor but binds to and inhibits CXC, CC, and C chemokines with low affinity... 

Lalani AS, Graham K, Mossman K et al. The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. J Virol 1997 71 4356. 

Cameron C, Hota-Mitchell S, Chen L et al. The complete DNA sequence of myxoma virus. Virology 1999 264 298-318. 

Upton C, Mossman K, McFadden G. Encoding of a homolog of the IFN-gamma receptor by myxoma virus. Science 1992 258 1369-1372. 

Mossman K, Upton C, McFadden G. The myxoma virus-soluble interferon-gamma receptor homolog, M-T7, inhibits interferon-gamma in a species-specific manner. J Biol Chem 1995 270 3031-3038. 

Mossman K, Nation P, Macen J et al. Myxoma virus M-T7, a secreted homolog of the interferon-gamma receptor, is a critical virulence factor for the development of myxomatosis in... 

Seet BT, Barrett J, Robichaud J et al. Glycosaminoglycan-binding properties of the myxoma virus CC-chemokine inhibitor, M-Tl. J Biol Chem 2001 21 21. 

Lalani AS, Masters J, Graham K et al. Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M- Tl, during myxoma virus pathogenesis. Virology 1999 256 233-245. 

Biological control of rabbits, using Myxoma virus, has been successful in Australia, where it was first undertaken. Although a moderate degree of resistance has now set in, the survivors are easily exterminated with sodium fluoro-acetate (non-selective). 

Douglas AE, Crabett KD, Berger JM, McFadden G, Handel TM. Struemre of M121L a myxoma virus stmctirral homolog of the apoptosis inhibitor, Bcl-2. Protein Sci. 

In some cases, poxvirus-encoded vTNFR homologues have additional properties in addition to the binding and inhibiting of TNF functions. This has been demonstrated in case of myxoma virus encoded M-T2 protein, which has a second anti-apoptotic role. In case of CrmE, it has recendy been shown that the protein also possesses chcmokinc binding properties. Thus, un-hke the engineered commercial TNF inhibitors currendy used in humans, the virus-encoded modulators sometime possess addidonal anti-inflammatory properties above and beyond just TNF inhibition. 

Xu X, Nash P, McFaddcn G. Myxoma virus expresses a TNF receptor homolog with two distinct functions. Virus Genes 2000 21(l-2) 97-109. 

Schreiber M, McFaddcn G. Ihc myxoma virus TNF-receptor homologue (T2) inhibits tumor necrosis factor-alpha in a species-specific fashion. Virology 1994 204(2) 692-705. 

Macen JL, Graham KA, Lee SF et aL Expression of the myxoma virus tumor necrosis fitetor receptor homologue and MllL genes is required to prevent virus-induced apoptosis in infected rabbit T-lymphocytes. Virology 1996 218(l) 232-237. 

Schreiber M, Sedger L, McFaddcn G. Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition. J Virol 1997 71(3) 2171-2181. 

In later studies, McFadden and Lomas demonstrated that the myxoma virus-encoded Serp-1 has sequence similarity to serpins, and the protein inhibits tPA, uPA and plasmin in the thrombolytic pathways as well as factor Xa in the thrombotic pathway. However, despite the marked effects of Serp-1 on viral pathogenesis, the Kj, for Serp-1 is a lower affinity reaction at 7-8.6 x 10 M s, whereas the manunalian serpin PAI-1 has higher affinity and activity with on the order... 

Spi-3 is a related but distina viral protein expressed by orthopoxviruses like vaccinia virus and rabbitpox, which unfortunately has a confosing nomenclature with similarity to the unrelated PI6/SPI3 mammalian scrpin nomenclature. Ihe poxviral Spi-3 binds to and inhibits uPA and tPA and plasmin. Spi-3 is also capable of formii weaker complexes with thrombin and factor Xa as measured by gel shifi assays. Spi-3 from vaccinia/rabbitpox and Serp-1 from myxoma virus share only 30% sequence similarity despite targeting similar host protease pathways. The Ki s for Spi-3 was measured as 0.51,1.9 and 0.64 nM for uPA, tPa and plasmin, respectively. The KjS for Serp-1 were similar at 0.16,0.14 and 0.44 nM, respectively for uPa, tPa and plasmin. However, whereas Serp-1 is secreted into the surrounding envirormient, Spi-3 remains tethered to the cell surface and exhibits a secondary function in the inhibition of cell fusion that is independent of its serpin-based activities. 

Upton QMaccnJL, Wishart OS ctaL Myxoma virus and malignant rabbit fibroma virus encode a serpin-like protein important for virus virulence. Virology 1990 179 618431. 

Macen JL, Upton C, Nation N et aL SERPl. a serine proteinase inhibitor encoded by myxoma virus, is a secreted ycrotein that interferes with inflammation. Virology 1993 195 348-363. 

Nash P, Whitty A, Handwerfccr J et aL Inhibitory specificity of the and-inflammatory myxoma virus serpin, serp-1. J Biol Chem 1998 27330982-20991. 

MacNcill AL, Turner PC, Moyer RW. Mutation of the myxoma virus serp-2 Pl-site to prevent proteinase inhibition causes apoptosis in cultured RK-13 cells and attenuates disease in rabbits, but mutation to alter specificity causes apoptosis without reducing virulence. Virology 2006 356 12-22. 

Messud Petit F, Gdfi J, Delverdier M et al. Setp-2, an inhibitor of the interleukin-lbeta-converting enzyme, is critical in the pathophysiology of myxoma virus. J Virol 1998 72 7830-7839. 

Nathaniel R, MacNeill AL, Wang YX et al. Cowpox virus CrmA, myxoma virus serp-2 and baculovirus P35 arc not fimctionally interchangeable caspase inhibitors in poxviras infections. J Gen Virol 2004 85 1267-1278. 

Upton C, Macen JL, Schreiber M et al. Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence. Virology 1991 184(l) 370-382. 

The 35-kDa protein or viral CC chemokine inhibitory protein (vCCI) is a secreted protein found in vaccinia virus (VACV) and other poxviruses that binds with high affinity almost all human and mouse CC chemokines [15-17]. The mechanism of action of the 35-kDa protein is competitive inhibition of CC chemokine binding to cellular receptors. The ortholog of myxoma virus (MYXV), named M-Tl, has the unique ability to interact with GAGs via a domain at its C-terminus that is not present in other 35-kDa family members [18]. This unique property of M-Tl would retain the protein in the vicinity of infected cells and may enhance its ability to protect the sites of infection from chemokine-mediated antiviral responses in vivo. Orf virus, a parapoxvirus that causes infections in sheep and cattle, and sporadically in humans, encodes a 35-kDa protein related vCKBP but with a broader chemokine binding specificity that includes the C chemokine lymphotactin [19]. 

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