Analysis of the Monkeypox Virus Genome

Щелкунов, С. Н.; Av, Totmenin; Safronov, Pavel F.; Mikheev, Maxim V.; Гуторов, В. В.; Ryazankina, O. I.; Petrov, Nikolai A.; Бабкин, И. В.; Уварова, Е. А.; Sandakhchiev, L. S.; Sisler, Jerry R.; Esposito, Joseph J.; Damon, Inger K.; Jahrling, Peter B.; Moss, Bernard

doi:10.1006/viro.2002.1446

Cited by 246 publications

(247 citation statements)

References 215 publications

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“…Here we demonstrate anti-TNF and antichemokine activities in the TNFR homologue CrmB encoded by VaV, define a protein domain (SECRET domain) that binds chemokines and uncover a previously undescribed family of secreted CrmB is the only predicted vTNFR active in VaV major and minor strains, which cause different fatality rates (1,(22)(23)(24), and in the four sequenced strains of monkeypox virus, which causes a smallpox-like disease in humans (22,25,26). Our demonstration that VaV CrmB is a potent inhibitor of TNF is consistent with previous evidence of down-regulation of TNF responses in an experimental macaque model of human smallpox (29).…”

Section: Discussionmentioning

confidence: 81%

“…VV Western Reserve and the strains used as smallpox vaccines Copenhagen, DryVax (Wyeth), and Tian-Tan, do not encode vTNFRs, but CrmC and CrmE are encoded by the vaccine strains Lister, USSR, and Evans (20,21). VaV and monkeypox virus, which causes a smallpox-like disease in humans, encode CrmB only (22)(23)(24)(25)(26). The reasons for the variety of vTNFRs are not understood.…”

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confidence: 99%

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A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

Alejo

Ruiz-Argüello

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

133

162

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Variola virus (VaV) is the causative agent of smallpox, one of the most devastating diseases encountered by man, that was eradicated in 1980. The deliberate release of VaV would have catastrophic consequences on global public health. However, the mechanisms that contribute to smallpox pathogenesis are poorly understood at the molecular level. The ability of viruses to evade the host defense mechanisms is an important determinant of viral pathogenesis. Here we show that the tumor necrosis factor receptor (TNFR) homologue CrmB encoded by VaV functions not only as a soluble decoy TNFR but also as a highly specific binding protein for several chemokines that mediate recruitment of immune cells to mucosal surfaces and the skin, sites of virus entry and viral replication at late stages of smallpox. CrmB binds chemokines through its C-terminal domain, which is unrelated to TNFRs, was named smallpox virus-encoded chemokine receptor (SECRET) domain and uncovers a family of poxvirus chemokine inhibitors. An active SECRET domain was found in another viral TNFR (CrmD) and three secreted proteins encoded by orthopoxviruses. These findings identify a previously undescribed chemokine-binding and inhibitory domain unrelated to host chemokine receptors and a mechanism of immune modulation in VaV that may influence smallpox pathogenesis.immune evasion ͉ viral pathogenesis ͉ cytokine receptor ͉ poxvirus ͉ inflammation

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Section: Discussionmentioning

confidence: 81%

mentioning

confidence: 99%

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

Alejo

Ruiz-Argüello

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

133

162

View full text Add to dashboard Cite

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“…Although complete genomic sequences have been determined for representative, and often multiple, viruses from classified chordopoxvirus (ChPV) genera infecting mammalian or avian hosts (Capripoxvirus [124,125], Leporipoxvirus [17,128], Molluscipoxvirus [106], Orthopoxvirus [5,7,24,44,49,76,108,109], Parapoxvirus [30], Suipoxvirus [4], Yatapoxvirus [14,68], and Avipoxvirus [3,123]), the CRV genome has not been characterized. Reptiles, considered to be the most immediate ancestor of birds and mammals, are poikilothermic animals with immune systems that remain relatively unstudied (13,32).…”

mentioning

confidence: 99%

Genome of Crocodilepox Virus

Afonso

Tulman

Delhon

et al. 2006

J Virol

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Here, we present the genome sequence, with analysis, of a poxvirus infecting Nile crocodiles (Crocodylus niloticus) (crocodilepox virus; CRV). The genome is 190,054 bp (62% G؉C) and predicted to contain 173 genes encoding proteins of 53 to 1,941 amino acids. The central genomic region contains genes conserved and generally colinear with those of other chordopoxviruses (ChPVs). CRV is distinct, as the terminal 33-kbp (left) and 13-kbp (right) genomic regions are largely CRV specific, containing 48 unique genes which lack similarity to other poxvirus genes. Notably, CRV also contains 14 unique genes which disrupt ChPV gene colinearity within the central genomic region, including 7 genes encoding GyrB-like ATPase domains similar to those in cellular type IIA DNA topoisomerases, suggestive of novel ATP-dependent functions. The presence of 10 CRV proteins with similarity to components of cellular multisubunit E3 ubiquitin-protein ligase complexes, including 9 proteins containing F-box motifs and F-box-associated regions and a homologue of cellular anaphasepromoting complex subunit 11 (Apc11), suggests that modification of host ubiquitination pathways may be significant for CRV-host cell interaction. CRV encodes a novel complement of proteins potentially involved in DNA replication, including a NAD ؉ -dependent DNA ligase and a protein with similarity to both vaccinia virus F16L and prokaryotic serine site-specific resolvase-invertases. CRV lacks genes encoding proteins for nucleotide metabolism. CRV shares notable genomic similarities with molluscum contagiosum virus, including genes found only in these two viruses. Phylogenetic analysis indicates that CRV is quite distinct from other ChPVs, representing a new genus within the subfamily Chordopoxvirinae, and it lacks recognizable homologues of most ChPV genes involved in virulence and host range, including those involving interferon response, intracellular signaling, and host immune response modulation. These data reveal the unique nature of CRV and suggest mechanisms of virus-reptile host interaction.

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“…Monkeypox virus (MPXV) is a member of the Orthopoxviridae family of poxviruses and is closely related to variola virus, the causative agent of smallpox (32). MPXV is endemic in the rainforests of central and western Africa and is believed to be primarily a zoonotic disease with sporadic infection of humans due to exposure to infected animals or animal tissues (17).…”

mentioning

confidence: 99%