Poxvirus Gene Expression and DNA Replication

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

↗ Live URL (may be dead)

Document text

Principal Investigator: Bernard  Moss
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $575,536
Funding agency: National Institute of Allergy and Infectious Diseases

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, mRNA biosynthesis and DNA synthesis. 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. Of the three transcription factors, only the early has been well studied. We are now investigating the intermediate and late factors. We previously determined that the intermediate factor is comprised of two subunits encoded by the A8 and A23 genes. Using the AlphaFold protein structure prediction program and the DALI structural similarity search, we found previously unknown homology to the eukaryotic transcription factor IIB and the TATA-binding protein, respectively. Furthermore, the Colabfold advanced prediction program suggests that the two subunits interact with a large space in the center that likely holds DNA. Efforts are now being made to confirm the functional interactions of the complex.

An understanding of the regulation of poxvirus gene expression and DNA replication will help to design vaccines and identify targets for antiviral therapy and will contribute to our understanding of these processes in other viruses and cells.

Terms: <Anabolism><Antiviral Therapy><Area><Basal Transcription Factor><Basal transcription factor genes><Biochemical Genetics><Cell Body><Cells><Complex><Consensus><Cytoplasm><DNA><DNA Replication><DNA Synthesis><DNA biosynthesis><DNA-Dependent RNA Polymerases><DNA-Directed RNA Polymerase><Deoxyribonucleic Acid><Enzyme Gene><Enzymes><Family><Focal Infection><GTF2B><GTF2B gene><Gene Action Regulation><Gene Expression><Gene Expression Regulation><Gene Regulation><Gene Regulation Process><Gene Transcription><General Transcription Factor Gene><General Transcription Factor IIB Gene><General Transcription Factor-IIB><General Transcription Factors><Genes><Genetic Transcription><Genome><Goals><Late Gene Transcriptions><Messenger RNA><Nucleic Acids><Poxviridae><Poxvirus officinale><Poxviruses><Process><Promoter Regions><Promotor Regions><Protein Analysis><Proteins><RNA Expression><RNA Polymerase II TATA-Binding Protein><RNA Polymerase II Transcription Factor IIB Gene><RNA Polymerase II Transcription Factor-IIB><RNA Polymerases><Reagent><Regulation><System><TATA Sequence-Binding Protein><TATA-Binding Protein><TATA-Box Binding Protein><TATA-Box Factor><TF2B Gene><TFIIB><TFIIB Gene><Transcription><Transcription Factor IIB Gene><Transcription Factor Proto-Oncogene><Transcription Factor TBP><Transcription Factor TFIIB><Transcription Factor-IIB><Transcription factor genes><Vaccine Design><Vaccinia virus><Viral><Virion><Virus><Virus Particle><anti-viral development><anti-viral drug development><anti-viral therapeutic development><anti-viral therapy><anti-viral therapy development><antiviral development><antiviral drug development><antiviral therapeutic development><antiviral therapy development><biosynthesis><developing anti-viral agent><developing anti-viral drug><developing anti-viral therapeutic><developing anti-viral therapy><developing antiviral agent><developing antiviral drug><developing antiviral therapeutic><developing antiviral therapy><genetic approach><genetic promoter element><genetic promoter sequence><genetic strategy><improved><infection localized><local infection><mRNA><member><plasmid vaccine><pox virus><poxvirus vectors><programs><promoter sequence><protein protein interaction><protein structure prediction><prototype><recombinant vaccinia virus><tissue culture><transcription factor><vector vaccine><viral infectious disease treatment>