The objective of this proposal is to identify the cis-acting signals involved in the replication and assembly of vesicular stomatitis virus (VSV). Two novel reverse genetic systems that allow directed manipulation of the VSV genome will be used to test several hypotheses proposed previously for how VSV replicates within host cells. The requirements for the assembly and release of VSV virions at the cell surface will also be examined. The first specific aim will examine the role of conserved sequences found at the 5' end of each VSV gene in gene expression. The second specific aim will examine the importance of an AU-rich sequence found at the 3' end of upstream genes on the expression of adjacent downstream genes. The third specific aim will examine sequences at the 5' end of the genomic RNA of VSV that are thought to contain a specific encapsidation signal required for nucleocapsid formation. The fourth specific aim will examine the effects of mutations in the G protein cytoplasmic domain on virus assembly and virus infectivity.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Chin, Jean
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University of Tennessee Health Science Center
Schools of Medicine
United States
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Whitt, Michael A (2010) Generation of VSV pseudotypes using recombinant ?G-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines. J Virol Methods 169:365-74
Perez, Mar; Clemente, Roberto; Robison, Clinton S et al. (2007) Generation and characterization of a recombinant vesicular stomatitis virus expressing the glycoprotein of Borna disease virus. J Virol 81:5527-36
Klas, Sheri D; Lavine, Christy L; Whitt, Michael A et al. (2006) IL-12-assisted immunization against Listeria monocytogenes using replication-restricted VSV-based vectors. Vaccine 24:1451-61
Duntsch, Christopher D; Zhou, Qihong; Jayakar, Himangi R et al. (2004) Recombinant vesicular stomatitis virus vectors as oncolytic agents in the treatment of high-grade gliomas in an organotypic brain tissue slice-glioma coculture model. J Neurosurg 100:1049-59
Pinschewer, Daniel D; Perez, Mar; Jeetendra, Eswaraka et al. (2004) Kinetics of protective antibodies are determined by the viral surface antigen. J Clin Invest 114:988-93
Miller, Mark A; Lavine, Christy L; Klas, Sheri D et al. (2004) Recombinant replication-restricted VSV as an expression vector for murine cytokines. Protein Expr Purif 33:92-103
Jeetendra, E; Ghosh, Kakoli; Odell, Derek et al. (2003) The membrane-proximal region of vesicular stomatitis virus glycoprotein G ectodomain is critical for fusion and virus infectivity. J Virol 77:12807-18
Klas, Sheri D; Robison, Clinton S; Whitt, Michael A et al. (2002) Adjuvanticity of an IL-12 fusion protein expressed by recombinant deltaG-vesicular stomatitis virus. Cell Immunol 218:59-73
Jeetendra, E; Robison, Clinton S; Albritton, Lorraine M et al. (2002) The membrane-proximal domain of vesicular stomatitis virus G protein functions as a membrane fusion potentiator and can induce hemifusion. J Virol 76:12300-11
Matsuura, Y; Tani, H; Suzuki, K et al. (2001) Characterization of pseudotype VSV possessing HCV envelope proteins. Virology 286:263-75

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