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.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2013
Total Cost
$640,709
Indirect Cost
City
State
Country
Zip Code
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
Sivan, Gilad; Ormanoglu, Pinar; Buehler, Eugen C et al. (2015) 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 6:
Reynolds, Sara E; Moss, Bernard (2015) Characterization of a large, proteolytically processed cowpox virus membrane glycoprotein conserved in most chordopoxviruses. Virology 483:209-17
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
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
Gjessing, Mona C; Yutin, Natalya; Tengs, Torstein et al. (2015) Salmon Gill Poxvirus, the Deepest Representative of the Chordopoxvirinae. J Virol 89:9348-67
Liu, Shin-Wu; Wyatt, Linda S; Orandle, Marlene S et al. (2014) The D10 decapping enzyme of vaccinia virus contributes to decay of cellular and viral mRNAs and to virulence in mice. J Virol 88:202-11
Sivan, Gilad; Martin, Scott E; Myers, Timothy G et al. (2013) Human genome-wide RNAi screen reveals a role for nuclear pore proteins in poxvirus morphogenesis. Proc Natl Acad Sci U S A 110:3519-24
Earl, Patricia L; Americo, Jeffrey L; Moss, Bernard (2012) Lethal monkeypox virus infection of CAST/EiJ mice is associated with a deficient gamma interferon response. J Virol 86:9105-12
Backes, Simone; Shapiro, Jillian S; Sabin, Leah R et al. (2012) Degradation of host microRNAs by poxvirus poly(A) polymerase reveals terminal RNA methylation as a protective antiviral mechanism. Cell Host Microbe 12:200-10

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