Abstract

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. Human genome-wide RNAi screens were conducted to determine host factors that impact poxvirus replication.

  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 #
1ZIAAI000979-14
Application #
10014116
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Liu, Ruikang; Moss, Bernard (2018) Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State. J Virol 92:
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
Sivan, Gilad; Ormanoglu, Pinar; Buehler, Eugen C et al. (2017) Erratum for Sivan et al., ""Identification of Restriction Factors by Human Genome-Wide RNA Interference Screening of Viral Host Range Mutants Exemplified by Discovery of SAMD9 and WDR6 as Inhibitors of the Vaccinia Virus K1L-C7L- Mutant"". MBio 8:
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

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