The parapoxvirus Orf virus ORF116 gene encodes an antagonist of the interferon response

• Published in: Journal of general virology Vol. 102; no. 12
• Main Authors: AlDaif, Basheer A, Mercer, Andrew A, Fleming, Stephen B
• Format: Journal Article
• Language: English
• Published: England 01.12.2021
• Subjects: Animals; Cell Line; Cytokines - immunology; Genes, Immediate-Early; Humans; Immunomodulation; Interferons - antagonists & inhibitors; Interferons - immunology; Mutation; Orf virus - genetics; Orf virus - immunology; Orf virus - metabolism; Sheep; Signal Transduction; Viral Proteins - genetics; Viral Proteins - immunology; poxvirus; Orf virus; immune modulation; interferon-stimulated genes; interferon
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/jgv.0.001695

Orf virus (ORFV) is the type species of the genus of the family. Genetic and functional studies have revealed ORFV has multiple immunomodulatory genes that manipulate innate immune responses, during the early stage of infection. is a novel gene of ORFV with hitherto unknown function. Characterization of an deletion mutant showed that it replicated in primary lamb testis cells with reduced levels compared to the wild-type and produced a smaller plaque phenotype. was shown to be expressed prior to DNA replication. The potential function of was investigated by gene-expression microarray analysis in HeLa cells infected with wild-type ORFV or the ORF116 deletion mutant. The analysis of differential cellular gene expression revealed a number of interferon-stimulated genes (ISGs) differentially expressed at either 4 or 6 h post infection. showed the greatest differential expression (4.17-fold) between wild-type and knockout virus. Other ISGs that were upregulated in the knockout included and and in addition the inflammatory cytokine . These findings were validated by infecting HeLa cells with an ORF116 revertant recombinant virus and analysis of transcript expression by quantitative real time-PCR (qRT-PCR). These observations suggested a role for the ORFV gene in modulating the IFN response and inflammatory cytokines. This study represents the first functional analysis of .