Effects of vaccinia virus uracil DNA glycosylase catalytic site and deoxyuridine triphosphatase deletion mutations individually and together on replication in active and quiescent cells and pathogenesis in mice

Silva, Frank S. De; Moss, Bernard

doi:10.1186/1743-422x-5-145

Cited by 20 publications

(20 citation statements)

References 52 publications

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“…5), suggesting that the latter protein is inactive and evolves towards degradation. Both viruses encode for a uracil DNA glycosylase, the other enzyme of critical importance to control the amount of uracil in DNA (De Silva and Moss, 2008). Whether Lausannevirus dUTPase is really active and results in metabolic and/or virulence differences with Marseillevirus such as in vaccinia virus (De Silva and Moss, 2008) remains to be determined.…”

Section: Resultsmentioning

confidence: 99%

Lausannevirus, a giant amoebal virus encoding histone doublets

Thomas

Bertelli

Collyn

et al. 2011

Environmental Microbiology

141

172

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Large viruses infecting algae or amoebae belong to the NucleoCytoplasmic Large DNA Viruses (NCLDV) and present genotypic and phenotypic characteristics that have raised major interest among microbiologists. Here, we describe a new large virus discovered in Acanthamoeba castellanii co-culture of an environmental sample. The virus, referred to as Lausannevirus, has a very limited host range, infecting Acanthamoeba spp. but being unable to infect other amoebae and mammalian cell lines tested. Within A. castellanii, this icosahedral virus of about 200 nm exhibits a development cycle similar to Mimivirus, with an eclipse phase 2 h post infection and a logarithmic growth leading to amoebal lysis in less than 24 h. The 346 kb Lausannevirus genome presents similarities with the recently described Marseillevirus, sharing 89% of genes, and thus belongs to the same family as confirmed by core gene phylogeny. Interestingly, Lausannevirus and Marseillevirus genomes both encode three proteins with predicted histone folds, including two histone doublets, that present similarities to eukaryotic and archaeal histones. The discovery of Lausannevirus and the analysis of its genome provide some insight in the evolution of these large amoebae-infecting viruses.

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Section: Resultsmentioning

confidence: 99%

Lausannevirus, a giant amoebal virus encoding histone doublets

Thomas

Bertelli

Collyn

et al. 2011

Environmental Microbiology

141

172

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show abstract

“…2B), showing that expression of the N-terminal region between residues 30 and 90 of the UNG2 protein is sufficient for modulation of the virus mutation rate. Interestingly, this region of UNG2 contains the determinants of the protein required for interaction with the p32 subunit of the RPA trimeric complex (12,28,30,31).…”

Section: Resultsmentioning

confidence: 99%

“…In vaccinia virus, the viral UNG is required for efficient virus replication in cultured cells, but viral UNG mutants lacking uracil-removal activity could efficiently replace the wt viral UNG for efficient virus replication in cultured cells (12,13,43). Moreover, deletion of UNG in CMV also resulted in a significant decrease of virus replication (35,36), but again, the uracil-excising activity of CMV UNG did not appear to be important for replication, since poor viral replication was unrelated to the uracil content of input genomes (38).…”

Section: Discussionmentioning

confidence: 99%

Recruitment of the Nuclear Form of Uracil DNA Glycosylase into Virus Particles Participates in the Full Infectivity of HIV-1

Guenzel

Hérate

Rouzic

et al. 2012

J Virol

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The HIV-1 Vpr protein participates in the early steps of the virus life cycle by influencing the accuracy of reverse transcription. This role of Vpr was related to the recruitment of the nuclear form of the uracil DNA glycosylase (UNG2) enzyme into virus particles, but several conflicting findings have been reported regarding the role of UNG2 encapsidation on viral infectivity. Here, we report that the catalytic activity of UNG2 was not required for influencing HIV-1 mutation, and this function of UNG2 was mapped within a 60-amino-acid domain located in the N-terminal region of the protein required for direct interaction with the p32 subunit of the replication protein A (RPA) complex. Importantly, enforced recruitment of overexpressed UNG2 into virions resulted in a net increase of virus infectivity, and this positive effect on infectivity was also independent of the UNG2 enzymatic activity. In contrast, virus infectivity and replication, as well as the efficiency of the viral DNA synthesis, were significantly reduced when viruses were produced from cells depleted of either endogenous UNG2 or RPA p32. Taken together, these results demonstrate that incorporation of UNG2 into virions has a positive impact on HIV-1 infectivity and replication and positively influences the reverse transcription process through a nonenzymatic mechanism involving the p32 subunit of the RPA complex.

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“…HFF were maintained as previously described (De Silva and Moss, 2008) and seeded into 6-well tissue culture plates in D-MEM supplemented with 10% FBS. When monolayers were confluent, culture medium was replaced with fresh medium supplemented with 0.2% FBS and maintained for 96 h to induce the resting state.…”

Section: Methodsmentioning

confidence: 99%

Cellular DNA Ligase I Is Recruited to Cytoplasmic Vaccinia Virus Factories and Masks the Role of the Vaccinia Ligase in Viral DNA Replication

Paran

Silva

Senkevich

et al. 2009

Cell Host & Microbe

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SUMMARY Vaccinia virus (VACV) encodes DNA polymerase and additional proteins that enable cytoplasmic replication. We confirmed the ability of VACV DNA ligase mutants to replicate and tested the hypothesis that cellular ligases compensate for loss of viral gene expression. Knock-down of human DNA ligase I but not other ligases with siRNA or a specific inhibitor severely reduced replication of viral DNA in cells infected with VACV ligase-deficient mutants, indicating that the cellular enzyme plays a complementary role. Replication of ligase-deficient VACV was greatly reduced and delayed in resting primary cells, correlating with initial low levels of ligase I and subsequent viral induction and localization of ligase I in virus factories. These studies indicate that DNA ligation is essential for poxvirus replication and explain the ability of ligase deletion mutants to replicate in dividing cells but exhibit decreased pathogenicity in mice. Encoding of a ligase might allow VACV to “jump-start” DNA synthesis.

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Effects of vaccinia virus uracil DNA glycosylase catalytic site and deoxyuridine triphosphatase deletion mutations individually and together on replication in active and quiescent cells and pathogenesis in mice

Cited by 20 publications

References 52 publications

Lausannevirus, a giant amoebal virus encoding histone doublets

Lausannevirus, a giant amoebal virus encoding histone doublets

Recruitment of the Nuclear Form of Uracil DNA Glycosylase into Virus Particles Participates in the Full Infectivity of HIV-1

Cellular DNA Ligase I Is Recruited to Cytoplasmic Vaccinia Virus Factories and Masks the Role of the Vaccinia Ligase in Viral DNA Replication

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