Regulation of Orthopoxvirus Gene Expression

Moss, Bernard

doi:10.1007/978-3-642-75605-4_2

Cited by 12 publications

(3 citation statements)

References 203 publications

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“…Poxvirus is the only known double-stranded DNA viral family that propagates in host cytoplasm and encodes most of the enzymes and factors necessary for transcription and replication of its material [ 35 ]. Once the virus enters into the host cytoplasm, it becomes uncoated to release its genetic information and component of early transcription system packaged within the core of the virion [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Monkeypox virus replication by RNA interference

Alkhalil

Strand

Mucker

et al. 2009

Virol J

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The Orthopoxvirus genus of Poxviridae family is comprised of several human pathogens, including cowpox (CPXV), Vaccinia (VACV), monkeypox (MPV) and Variola (VARV) viruses. Species of this virus genus cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. In this study, we investigated the potential of RNA interference pathway (RNAi) as a therapeutic approach for orthopox virus infections using MPV as a model. Based on genome-wide expression studies and bioinformatic analysis, we selected 12 viral genes and targeted them by small interference RNA (siRNA). Fortyeight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were limiting to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R) or an important gene in viral entry (E8L), inhibited viral replication in cell culture by 65-95% with no apparent cytotoxicity. Further analysis with wild-type and recombinant MPV expressing green fluorescence protein demonstrated that one of these constructs, siA6-a, was the most potent and inhibited viral replication for up to 7 days at a concentration of 10 nM. These results emphasis the essential role of A6R gene in viral replication, and demonstrate the potential of RNAi as a therapeutic approach for developing oligonucleotidebased drug therapy for MPV and other orthopox viruses.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Monkeypox virus replication by RNA interference

Alkhalil

Strand

Mucker

et al. 2009

Virol J

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“…The infectious cycle involves successive temporally regulated events of early gene expression, DNA replication, late gene expression, and morphogenesis. The progression of virus replication is virtually controlled by virus-encoded factors and many of these genes have already been identified [29].…”

Section: Introductionmentioning

confidence: 99%

Cyclosporin A inhibits vaccinia virus replication in vitro

Damaso

Keller

1994

Archives of Virology

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The effect of the immune modulator, Cyclosporin A (CsA) on vaccinia virus replication has been examined in cell cultures. In the present study we report that CsA is anti-viral towards vaccinia virus. Viral yield was inhibited by more than 97% after 24 h postinfection in the presence of 16 microM to 40 microM CsA. An analysis of the infectious cycle in greater detail revealed that CsA did not effect the total level of [35S] methionine incorporation into vaccinia infected cells. However, both early and late viral gene expression were inhibited by CsA. Late viral protein synthesis appeared to be more sensitive to the drug. At least one late viral polypeptide of approximately Mr 38,000 was virtually undetected up to 8 h postinfection in the presence of 40 microM CsA. Host protein synthesis which is normally inhibited by the virus was not turned off until very late in infection. Viral DNA replication was also inhibited by the addition of CsA at levels comparable to those observed for late protein synthesis.

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“…Its genome is formed by a double-stranded DNA molecule of about 170 kbp with hairpin loops and terminal inverted repeats (Gonzfilez et al, 1986;Sogo et al, 1984), similar to those of poxvirus DNA (Baroudy et al, 1982;Wittek & Moss, 1980). Like the poxviruses (Moss, 1990), ASF virus packages a complete enzymatic system for the synthesis of early RNA (Kuznar et al, 1980;Salas et al, 1981Salas et al, , 1986.…”

mentioning

confidence: 99%

African swine fever virus thymidylate kinase gene: sequence and transcriptional mapping

Yáñez

Rodríguez²,

Rodrı́guez³

et al. 1993

Journal of General Virology

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A putative thymidylate kinase gene of African swine fever virus has been identified at the left end of the Sall I' fragment of the virus genome. The gene, designated A240L, has the potential to encode a protein of 240 amino acids with an M r of 27 754 and is transcribed early after infection. Primer extension analysis indicates that transcription is initiated a short distance from the first ATG codon of open reading frame A240L. The deduced amino acid sequence of this open reading frame shows significant similarity with the human, yeast and vaccinia virus thymidylate kinases, the degree of identity being 23"7, 25 and 23"5 %, respectively. The putative African swine fever virus thymidylate kinase sequence is essentially collinear with the other thymidylate kinase sequences, but contains a carboxy-terminal extension of 37 amino acids rich in glutamic and aspartic acids. The A240L protein conserves the ATP-binding and nucleotide/nucleoside-binding domains characteristic of thymidylate kinases.

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Regulation of Orthopoxvirus Gene Expression

Cited by 12 publications

References 203 publications

Inhibition of Monkeypox virus replication by RNA interference

Inhibition of Monkeypox virus replication by RNA interference

Cyclosporin A inhibits vaccinia virus replication in vitro

African swine fever virus thymidylate kinase gene: sequence and transcriptional mapping

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