Interferons are a family of proteins with a variety of biological activities including antiviral and anticellular activities. Although it is known that all actions of interferons are mediated by the products of interferon-inducible genes, the detailed mechanisms of actions of interferons have not been elucidated as yet. In this project, mechanisms of antiviral actions of interferons will be investigated. Specifically, how interferons inhibit the replication of vesicular stomatitis virus, of encephalomyocarditis virus and of retroviruses will be the subject of investigation. Which interferon-inducible gene product is responsible for which antiviral action and how and where in the viral life-cycle the interferon-mediated block is exerted are among the question to be asked. For these purpose, advantage will be taken of partially interferon-responsive cell clones isolated by us in which replication of one virus but not of another is inhibited by interferons. The role of a ribonuclease activity associated with subviral particles isolated from interferon-treated cells in inhibiting vesicular stomatitis viral primary transcription will be evaluated. Whether interferons can inhibit replication of encephalomyocarditis virus without using the ribonuclease L pathway will be investigated and at what step of retroviral DNA synthesis and integration the interferon-mediated block is will be determined.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Cleveland Clinic Lerner
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Desai, S Y; Patel, R C; Sen, G C et al. (1995) Activation of interferon-inducible 2'-5' oligoadenylate synthetase by adenoviral VAI RNA. J Biol Chem 270:3454-61
Patel, R C; Stanton, P; McMillan, N M et al. (1995) The interferon-inducible double-stranded RNA-activated protein kinase self-associates in vitro and in vivo. Proc Natl Acad Sci U S A 92:8283-7
Patel, R C; Stanton, P; Sen, G C (1994) Role of the amino-terminal residues of the interferon-induced protein kinase in its activation by double-stranded RNA and heparin. J Biol Chem 269:18593-8
Wu, C; Ohmori, Y; Bandyopadhyay, S et al. (1994) Interferon-stimulated response element and NF kappa B sites cooperate to regulate double-stranded RNA-induced transcription of the IP-10 gene. J Interferon Res 14:357-63
Patel, R C; Sen, G C (1994) Characterization of the interactions between double-stranded RNA and the double-stranded RNA binding domain of the interferon induced protein kinase. Cell Mol Biol Res 40:671-82
Sen, G C; Ransohoff, R M (1993) Interferon-induced antiviral actions and their regulation. Adv Virus Res 42:57-102
Kalvakolanu, D V; Sen, G C (1993) Differentiation-dependent activation of interferon-stimulated gene factors and transcription factor NF-kappa B in mouse embryonal carcinoma cells. Proc Natl Acad Sci U S A 90:3167-71
Patel, R C; Sen, G C (1992) Construction and expression of an enzymatically active human-mouse chimeric double-stranded RNA-dependent protein kinase. J Interferon Res 12:389-93
Patel, R C; Sen, G C (1992) Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. J Biol Chem 267:7671-6
Bandyopadhyay, S K; Sen, G C (1992) Role of protein phosphorylation in activation of interferon-stimulated gene factors. J Biol Chem 267:6389-95

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