MALDI-TOF mass spectroscopy detects the capsid structural instabilities created by deleting the myxoma virus cupro-zinc SOD1 homolog M131R

Zachertowska, Alicja; Brewer, Dyanne; Evans, David H.

doi:10.1016/j.jviromet.2004.08.004

Cited by 9 publications

(9 citation statements)

References 19 publications

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“…LSDV_131 encodes a homolog of a catalytically inactive poxvirus Cu‐Zn superoxide dismutase. The leporipoxvirus homologs of this protein modulate superoxide signalling and are also major capsid components that affect virus sensitivity to thermal stress (Teoh, Turner, & Evans, ; Zachertowska, Brewer, & Evans, ).…”

Section: Resultsmentioning

confidence: 99%

“…This family of LSDV vaccine isolates also all encode a deletion in the superoxide dismutase homolog LSDV_131. Its homolog has been shown to play a role in stabilizing leporipoxvirus particles against thermal stress (Zachertowska et al, ), and such a mutation may not be desirable in a vaccine where a cold chain cannot be guaranteed. Many spontaneous mutations in poxviruses can be traced to small repeats and duplications (Qin, Upton, Hazes, & Evans, ), and the same pattern is detected in these vaccine isolates especially at A/T‐rich regions.…”

Section: Discussionmentioning

confidence: 99%

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Extended sequencing of vaccine and wild‐type capripoxvirus isolates provides insights into genes modulating virulence and host range

Biswas

Noyce

Babiuk

et al. 2019

Transbound Emerg Dis

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The genus Capripoxvirus in the subfamily Chordopoxvirinae, family Poxviridae, comprises sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin disease virus (LSDV), which cause the eponymous diseases across parts of Africa, the Middle East and Asia. These diseases cause significant economic losses and can have a devastating impact on the livelihoods and food security of small farm holders. So far, only live classically attenuated SPPV, GTPV and LSDV vaccines are commercially available and the history, safety and efficacy of many have not been well established. Here, we report 13 new capripoxvirus genome sequences, including the hairpin telomeres, from both pathogenic field isolates and vaccine strains. We have also updated the genome annotations to incorporate recent advances in our understanding of poxvirus biology. These new genomes and genes grouped phenetically with other previously sequenced capripoxvirus strains, and these new alignments collectively identified several recurring alterations in genes thought to modulate virulence and host range. In particular, some of the many large capripoxvirus ankyrin and kelch‐like proteins are commonly mutated in vaccine strains, while the variola virus B22R‐like gene homolog has also been disrupted in many vaccine isolates. Among these vaccine isolates, frameshift mutations are especially common and clearly present a risk of reversion to wild type in vaccines bearing these mutations. A consistent pattern of gene inactivation from LSDV to GTPV and then SPPV is also observed, much like the pattern of gene loss in orthopoxviruses, but, rather surprisingly, the overall genome size of ~150 kbp remains relatively constant. These data provide new insights into the evolution of capripoxviruses and the determinants of pathogenicity and host range. They will find application in the development of new vaccines with better safety, efficacy and trade profiles.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Extended sequencing of vaccine and wild‐type capripoxvirus isolates provides insights into genes modulating virulence and host range

Biswas

Noyce

Babiuk

et al. 2019

Transbound Emerg Dis

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“…To directly test the binding of MYXV and VACV to different cell types and under different conditions, we have constructed fluorescently tagged versions of MYXV and VACV and then compared the binding and infection of these viruses to various human normal and cancerous cells. To this end, we constructed a recombinant MYXV in which the M093L gene (the ortholog of the VAC A4L IMV structural protein [11,33]) was replaced with the M093L gene fused with the coding sequence of fluorescent protein Venus at the amino terminus. This new recombinant virus (vMyx-Venus/M093) expresses Venus-fused M093 as a tagged virion component.…”

mentioning

confidence: 99%

Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Chan

Bartee²,

Moreb

et al. 2013

J Virol

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“…We suspect that the phenomenon reflects a role served by the protein in stabilizing the capsid against environmental stressors like desiccation and heat. Such a function is not required under laboratory growth and infection conditions and might conceivably have detrimental effects on virus yields (57). We have also shown that deleting the SFV S131R gene renders SFV less "tumorigenic" in rabbits and that these gene products play a role in suppressing Fas-and staurosporine-triggered apoptosis in cultured cells.…”

Section: Discussionmentioning

confidence: 83%

“…The gene is clearly dispensable for virus replication in tissue culture and, like M131R-deficient MYX strains, the size and morphology of the foci formed by VMLT1.6 virus on SIRC cells were indistinguishable from those of the SFV-WT and R-S131R strains (data not shown). The S131R-deficient SFV virions also shared with mutant MYX strains some thermolability at elevated (55°C) temperatures (57). Perhaps the most interesting property of these viruses, and one that again characterizes M131R⌬ MYX virus (9), is that deleting the S131R gene enhances the yield of SFV.…”

Section: Resultsmentioning

confidence: 98%

Tumorigenic Poxviruses Up-Regulate Intracellular Superoxide To Inhibit Apoptosis and Promote Cell Proliferation

Teoh

Turner

Evans

2005

J Virol

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Tumorigenic leporipoxviruses encode catalytically inactive homologs of cellular Cu-Zn superoxide dismutase (SOD1). The function of the orthologous myxoma virus M131R and Shope fibroma virus S131R gene products is uncertain, but they inhibit SOD1 activity by a process linked to binding its copper chaperone. Using a superoxide-sensitive dye (hydroethidine), we observed that virus infection increased intracellular superoxide levels in an M/S131R-dependent manner. To see whether this effect promotes infection, we deleted the Shope fibroma virus S131R gene and compared the clinical manifestations of wild-type and mutant virus infections in rabbits. S131R⌬ virus produced significantly smaller fibroxanthosarcoma-like growths in vivo and, at a point where these growths were already receding, wild-type infections still showed extensive leukocyte infiltration, necrosis, and fibromatous cell proliferation. Coincidentally, whereas Jurkat cells are protected from mitochondria-and Fas-mediated apoptosis by wild-type myxoma virus in vitro, M131R⌬ virus could not block Fas-initiated apoptosis as judged by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTPfluorescein nick end labeling, and caspase 3 cleavage assays. These data suggest that tumorigenic poxviruses can modulate intracellular redox status to their advantage to stimulate infected cell growth and inhibit programmed cell death.

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MALDI-TOF mass spectroscopy detects the capsid structural instabilities created by deleting the myxoma virus cupro-zinc SOD1 homolog M131R

Cited by 9 publications

References 19 publications

Extended sequencing of vaccine and wild‐type capripoxvirus isolates provides insights into genes modulating virulence and host range

Extended sequencing of vaccine and wild‐type capripoxvirus isolates provides insights into genes modulating virulence and host range

Myxoma and Vaccinia Viruses Bind Differentially to Human Leukocytes

Tumorigenic Poxviruses Up-Regulate Intracellular Superoxide To Inhibit Apoptosis and Promote Cell Proliferation

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