Poxvirus Gene Expression

Moss, Bernard

Abstract

Poxviruses encode enzymes and factors needed for transcription and replication of their genomes within the cytoplasm of infected cells. Vaccinia virus, the prototypic member of the poxvirus family, provides a unique system for combining biochemical and genetic approaches for investigating mechanisms of gene regulation and mRNA biosynthesis. Studies with vaccinia virus indicated that the genes are divided into three temporal classes - early, intermediate and late. Each gene class has a consensus DNA promoter sequence and corresponding transcription factors that interact with the virus-encoded multisubunit RNA polymerase. The transcription system for early genes is packaged within the infectious virus particle during its assembly, whereas the factors for intermediate and late gene transcription are synthesized successively after infection and localize within cytoplasmic factory areas. Poxviruses also encode enzymes that modify their mRNA by adding a cap structure to the 5'end and a poly(A) tail to the 3'end, which are necessary for efficient translation and stability. The shut down of cellular protein synthesis and the tight regulation of viral protein synthesis are regulated by poxvirus enzymes that cleave the cap structure. Using new generation DNA sequencing, we have made a complete transcription map of the vaccinia virus genome and defined the RNA start sites and the sequences adjacent to the poly(A) tail. These studies have revealed numerous previously unannotated transcripts. In addition, the effects of vaccinia virus infection on host mRNAs have been defined.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI000307-32
• Application #: 8745281
• Support Year: 32
• Fiscal Year: 2013
• Total Cost: $640,709

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Stuart, Carey A; Zhivkoplias, Erik K; Senkevich, Tatiana G et al. (2018) RNA polymerase mutations selected during experimental evolution enhance replication of a hybrid vaccinia virus with an intermediate transcription factor subunit replaced by the myxoma virus ortholog. J Virol :

Liu, Baoming; Panda, Debasis; Mendez-Rios, Jorge D et al. (2018) Identification of Poxvirus Genome Uncoating and DNA Replication Factors with Mutually Redundant Roles. J Virol 92:

Senkevich, Tatiana G; Katsafanas, George; Weisberg, Andrea et al. (2017) Identification of Vaccinia Virus Replisome and Transcriptome Proteins by iPOND Coupled with Mass Spectrometry. J Virol :

Moss, Bernard (2017) Investigating Viruses during the Transformation of Molecular Biology. J Biol Chem 292:3958-3969

Mendez-Rios, Jorge D; Yang, Zhilong; Erlandson, Karl J et al. (2016) Molluscum Contagiosum Virus Transcriptome in Abortively Infected Cultured Cells and a Human Skin Lesion. J Virol 90:4469-80

Senkevich, Tatiana G; Bruno, Daniel; Martens, Craig et al. (2015) Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing. Proc Natl Acad Sci U S A :

Gjessing, Mona C; Yutin, Natalya; Tengs, Torstein et al. (2015) Erratum for Gjessing et al., Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. J Virol 89:11174

Yang, Zhilong; Moss, Bernard (2015) Decoding poxvirus genome. Oncotarget 6:28513-4

Yang, Zhilong; Cao, Shuai; Martens, Craig A et al. (2015) Deciphering poxvirus gene expression by RNA sequencing and ribosome profiling. J Virol 89:6874-86

Gjessing, Mona C; Yutin, Natalya; Tengs, Torstein et al. (2015) Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. J Virol 89:9348-67