Genome Variability and Gene Content in Chordopoxviruses: Dependence on Microsatellites

Hatcher, Eneida L.; Wang, Chunlin; Lefkowitz, Elliot J.

doi:10.3390/v7042126

Cited by 23 publications

(22 citation statements)

References 50 publications

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“…The EKPV-NSW genome has a relatively high GC (57.7%) content compared to recently isolated KPVs (54%), as well as other chordopoxviruses which range from 25–67% 34 , although, the biological significance for this variation is not yet known. High GC ratio poxviruses include those belonging to the molluscipoxvirus, Crocodylidpoxvirus and Parapoxvirus 35 , which might explain further why EKPV-NSW showed the second highest similarity with the Molluscum contagiosum virus, Nile crocodilepox virus and Squirrel poxvirus . Studies by Hatcher et al .…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Sarker

Roberts

Tidd

et al. 2017

Sci Rep

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Poxviruses are large DNA viruses with varying zoonotic potential, and are recognised in a broad range of wildlife. Although poxviruses have been detected in kangaroos, their genetic relationships to poxviruses in other animals and humans is not well understood. Here, we present a novel genome sequence of a marsupial poxvirus, the Eastern grey kangaroopox virus (EKPV-NSW), isolated from a wild eastern grey kangaroo. In the present study, histopathologically confirmed epidermal pox lesions were used to recover the full-length viral genome and perform electron microscopic analysis, with both immature virions and intracellular mature virions detected. Subsequent analysis of the EKPV-NSW genome demonstrated the highest degree of sequence similarity with EKPV-SC strain (91.51%), followed by WKPV-WA (87.93%), and MOCV1 (44.05%). The novel EKPV-NSW complete genome encompasses most of the chordopoxviruses protein coding genes (138) that are required for genome replication and expression, with only three essential protein coding genes being absent. The novel EKPV-NSW is missing 28 predicted genes compared to the recently isolated EKPV-SC, and carries 21 additional unique genes, encoding unknown proteins. Phylogenetic and recombination analyses showed EKPV-NSW to be the distinct available candidate genome of chordopoxviruses.

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Section: Discussionmentioning

confidence: 99%

“…Studies by Hatcher et al . 35 also postulated that high GC ratio viruses may be subject to different evolutionary mechanisms, including a lack of gene reduction as compared to viruses with higher AT content.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Sarker

Roberts

Tidd

et al. 2017

Sci Rep

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“…Lipophilicity largely dictates the binding of bisbenzimides to double-stranded DNA via hydrophobic interactions with adenosine-threonine (A = T)-rich regions ( 25 , 59 , 60 ). Since poxviruses with differential genomic A = T content—that is VACV (67% A = T), ORFV (36% A = T), and SQPV (33% A = T) ( 61 )—display similar sensitivities to H4, it is unlikely that poxviruses are susceptible to bisbenzimides simply due to their high A = T content. It is more likely that the solute accessibility of the viral genome and the association of DNA binding proteins dictate susceptibility of the virus to the Hoechst compounds.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives

Yakimovich

Huttunen

Zehnder

et al. 2017

J Virol

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Virus infection of humans and livestock can be devastating for individuals and populations, sometimes resulting in large economic and societal impact. Prevention of virus disease by vaccination or antiviral agents is difficult to achieve. A notable exception was the eradication of human smallpox by vaccination over 30 years ago. Today, humans and animals remain susceptible to poxvirus infections, including zoonotic poxvirus transmission. Here we identified a small molecule, bisbenzimide (bisbenzimidazole), and its derivatives as potent agents against prototypic poxvirus infection in cell culture. We show that bisbenzimide derivatives, which preferentially bind the minor groove of double-stranded DNA, inhibit vaccinia virus infection by blocking viral DNA replication and abrogating postreplicative intermediate and late gene transcription. The bisbenzimide derivatives are potent against vaccinia virus and other poxviruses but ineffective against a range of other DNA and RNA viruses. The bisbenzimide derivatives are the first inhibitors of their class, which appear to directly target the viral genome without affecting cell viability.IMPORTANCE Smallpox was one of the most devastating diseases in human history until it was eradicated by a worldwide vaccination campaign. Due to discontinuation of routine vaccination more than 30 years ago, the majority of today's human population remains susceptible to infection with poxviruses. Here we present a family of bisbenzimide (bisbenzimidazole) derivatives, known as Hoechst nuclear stains, with high potency against poxvirus infection. Results from a variety of assays used to dissect the poxvirus life cycle demonstrate that bisbenzimides inhibit viral gene expression and genome replication. These findings can lead to the development of novel antiviral drugs that target viral genomes and block viral replication.

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“…These so-called microsatellites can be found throughout the whole poxvirus genome, accounting for about 24% of the sequence [ 47 ]. Previously, early stop mutations were found to be accumulated in chordopoxvirus microsatellites, leading to the hypothesis of microsatellite hypervariability as a major source of poxvirus genome variability and hence as a source of poxvirus adaptation [ 47 ]. Our data suggests that hypervariability in microsatellites is a CPXV adaptation mechanism in cell culture.…”

Section: Discussionmentioning

confidence: 99%

Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism

Grossegesse

Doellinger

Tyshaieva

et al. 2017

Viruses

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DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Subsequently, we analyzed the proteome and genome of the non-passaged virions and each passage. While the overall viral genome sequence was stable during passaging, proteomics revealed multiple changes in the virion composition. Interestingly, an increased viral fitness in human cells was observed in the presence of increased immunomodulatory protein amounts. As the only minor variant with increasing frequency during passaging was located in a viral RNA polymerase subunit and, moreover, most minor variants were found in transcription-associated genes, protein amounts were presumably regulated at transcription level. This study is the first comparative proteome analysis of virus particles before and after cell culture propagation, revealing proteomic changes as a novel poxvirus adaptation mechanism.

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Genome Variability and Gene Content in Chordopoxviruses: Dependence on Microsatellites

Cited by 23 publications

References 50 publications

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Inhibition of Poxvirus Gene Expression and Genome Replication by Bisbenzimide Derivatives

Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism

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