Research:
Pathogenesis of Mumps Virus

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 work 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 PIV5, 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. We hypothesize 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 PIV5 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 (rMuVĢSH) will be generated and (3) compared with its parental mumps virus in tissue culture cells and in a rat model system.