Mumps virus causes acute infections in humans and about 10% of infection leads to aseptic meningitis. Although several mumps virus genome sequences are known, molecular bases of mumps virus pathogenesis are not clear. Long-term goal of this proposal is to understand how virus overcomes host defense mechanisms, especially how viral proteins overcome host innate immunity at molecular levels in tissue culture cells as well as in animals. The small hydrophobic protein (SH) of simian virus 5 (SV5), a virus closely related to mumps virus, plays an important role in inhibiting tumor necrosis factor (TNF)-alpha activated apoptotic pathway and the deletion of SH results in an attenuated virus in vivo. It is hypothesized that inhibition of apoptosis by virus-infected cells contributes to viral pathogenesis and mumps virus small hydrophobic protein (SH) plays essential roles in inhibition of cell death in virus-infected cells like SH of SV5 even though both SH proteins have no sequence homologies. To test these hypothesis, (1) a reverse genetics system in which infectious mumps virus from cDNA of a clinical isolate will be obtained will be established, (2) mumps virus lacking SH gene (rMuVdeltaSH) will be generated and (3) compared with its parental mumps virus in tissue culture cells and in a rat model system. Since my joining Penn State University in 2001 as a tenure-track assistant professor of virology, we have identified pathways leading to apoptosis in SV5 lacking SH (rSV5deltaSH) or in SV5 lacking the conserved C-terminus of V (rSVSVdeltaC)- infected cells. I hope to establish a research program in understanding the relationship between pathogenicity of mumps virus and functions of individual mumps virus proteins. The proposed work in this application builds on our current work on paramyxovirus SV5 SH function, expands our current work from SV5 SH to mumps virus SH and redirects our focus on functions of viral proteins in tissue culture system to that in an animal model system as well as in tissue culture cells.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Scientist Development Award - Research (K02)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Cassetti, Cristina
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Pennsylvania State University
Veterinary Sciences
Schools of Earth Sciences/Natur
University Park
United States
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Xu, Pei; Luthra, Priya; Li, Zhuo et al. (2012) The V protein of mumps virus plays a critical role in pathogenesis. J Virol 86:1768-76
Sun, Dengyun; Luthra, Priya; Xu, Pei et al. (2011) Identification of a phosphorylation site within the P protein important for mRNA transcription and growth of parainfluenza virus 5. J Virol 85:8376-85
Sun, Dengyun; Xu, Pei; He, Biao (2011) Sumoylation of the P protein at K254 plays an important role in growth of parainfluenza virus 5. J Virol 85:10261-8
Li, Zhuo; Xu, Jie; Patel, Jui et al. (2011) Function of the small hydrophobic protein of J paramyxovirus. J Virol 85:32-42
Xu, Pei; Li, Zhuo; Sun, Dengyun et al. (2011) Rescue of wild-type mumps virus from a strain associated with recent outbreaks helps to define the role of the SH ORF in the pathogenesis of mumps virus. Virology 417:126-36
Fuentes, Sandra M; Sun, Dengyun; Schmitt, Anthony P et al. (2010) Phosphorylation of paramyxovirus phosphoprotein and its role in viral gene expression. Future Microbiol 5:9-13
Li, Ming; Schmitt, Phuong Tieu; Li, Zhuo et al. (2009) Mumps virus matrix, fusion, and nucleocapsid proteins cooperate for efficient production of virus-like particles. J Virol 83:7261-72
Sun, Dengyun; Luthra, Priya; Li, Zhuo et al. (2009) PLK1 down-regulates parainfluenza virus 5 gene expression. PLoS Pathog 5:e1000525
Cox, Robert; Green, Todd J; Qiu, Shihong et al. (2009) Characterization of a mumps virus nucleocapsidlike particle. J Virol 83:11402-6
Timani, Khalid A; Sun, Dengyun; Sun, Minghao et al. (2008) A single amino acid residue change in the P protein of parainfluenza virus 5 elevates viral gene expression. J Virol 82:9123-33

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