Poxviruses comprise a large family of complex DNA viruses that have vertebrate and invertebrate hosts. Two poxviruses, variola virus and molluscum contagiosum virus, are specific human pathogens. Variola virus was the cause of smallpox until the latter was eradicated but is still feared because of potential use a biological weapon. Molluscum contagiosum virus causes benign skin lesions in immunocompetent infants and a more severe and widespread disease in immunodeficient adults. In addition, several animal poxviruses can be transmitted to humans as zoonosis. The most serious of these is monkeypox, which has an estimated human mortality of 1 to 10%. The poxviruses express a large number of host immune evasion genes that contribute to virulence. The purpose of this project is to increase our understanding of poxvirus pathogenesis and the basis for immunity to poxviruses.A human genome-wide RNAi screen was conducted to determine host factors that impact poxvirus replication.

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9
Fiscal Year
2014
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Cotter, Catherine A; Earl, Patricia L; Wyatt, Linda S et al. (2017) Preparation of Cell Cultures and Vaccinia Virus Stocks. Curr Protoc Protein Sci 89:5.12.1-5.12.18
Americo, Jeffrey L; Earl, Patricia L; Moss, Bernard (2017) Droplet digital PCR for rapid enumeration of viral genomes and particles from cells and animals infected with orthopoxviruses. Virology 511:19-22
Reynolds, Sara E; Earl, Patricia L; Minai, Mahnaz et al. (2017) A homolog of the variola virus B22 membrane protein contributes to ectromelia virus pathogenicity in the mouse footpad model. Virology 501:107-114
Cotter, Catherine A; Earl, Patricia L; Wyatt, Linda S et al. (2017) Preparation of Cell Cultures and Vaccinia Virus Stocks. Curr Protoc Mol Biol 117:16.16.1-16.16.18
Earl, Patricia L; Americo, Jeffrey L; Moss, Bernard (2017) Insufficient Innate Immunity Contributes to the Susceptibility of the Castaneous Mouse to Orthopoxvirus Infection. J Virol 91:
Panda, Debasis; Fernandez, Daniel J; Lal, Madhu et al. (2017) Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants. Proc Natl Acad Sci U S A 114:3720-3725
Liu, Ruikang; Moss, Bernard (2016) Opposing Roles of Double-Stranded RNA Effector Pathways and Viral Defense Proteins Revealed with CRISPR-Cas9 Knockout Cell Lines and Vaccinia Virus Mutants. J Virol 90:7864-79
Earl, Patricia L; Americo, Jeffrey L; Moss, Bernard (2015) Genetic studies of the susceptibility of classical and wild-derived inbred mouse strains to monkeypox virus. Virology 481:161-5
Earl, Patricia L; Americo, Jeffrey L; Cotter, Catherine A et al. (2015) Comparative live bioluminescence imaging of monkeypox virus dissemination in a wild-derived inbred mouse (Mus musculus castaneus) and outbred African dormouse (Graphiurus kelleni). Virology 475:150-8
Liu, Shin-Wu; Katsafanas, George C; Liu, Ruikang et al. (2015) Poxvirus decapping enzymes enhance virulence by preventing the accumulation of dsRNA and the induction of innate antiviral responses. Cell Host Microbe 17:320-31

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