Herpesvirus infections of humans are among the most common of all human infections and can result in life-threatening diseases, although infrequently. This family of viruses is of great scientific interest because of their prevalence and unique propensity to establish latency and recur, even in the presence of humoral antibodies and cell mediated immunity. We have demonstrated that cloned human interferons (IFNs) block herpes simplex virus type 1 (HSV-1) replication at the stage of virus assembly and budding, probably through specific inhibition of viral glycoproteins. In addition, we have also suggested that these IFNs block HSV-1-mediated cell fusion via a similar mechanism. The goals of this project are to obtain a detailed understanding of how recombinant human IFNs affect the expression of specific HSV-glycoproteins such that these two important biological functions, replication and cell fusion, are prevented. First the viral glycoprotein synthesis and the expression and structure of viral glycoprotein mRNAs in IFN-treated cells will be analysed in order to pinpoint the exact nature of the glycoprotein inhibition in IFN-treated cells. Second, immunological and biochemical experiments will be performed to demonstrate the location of specific HSV-glycoprotein(s) in IFN-treated in comparison to untreated cells. Finally, the roles of glycoproteins in viral assembly and in induction of cell fusion will be studied through mammalian cell lines expressing cloned glycoprotein genes and by the analysis of deletion mutants in these glycoprotein genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI025120-02
Application #
3454331
Study Section
Experimental Virology Study Section (EVR)
Project Start
1987-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
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Langford, C K; Ullman, B; Landfear, S M (1992) Leishmania: codon utilization of nuclear genes. Exp Parasitol 74:360-1
Chatterjee, S; Sarkar, S (1992) Studies on endoplasmic reticulum--Golgi complex cycling pathway in herpes simplex virus-infected and brefeldin A-treated human fibroblast cells. Virology 191:327-37
Nielsen, L N; Whitley, R J; Chatterjee, S (1991) Apical expression of herpes simplex virus type 2 glycoproteins in human neuroblastoma cells. Virology 185:908-10
Chatterjee, S; Burns, P (1990) Expression of herpes simplex virus type 1 glycoproteins in interferon-treated human neuroblastoma cells. J Virol 64:5209-13
Chatterjee, S; Nishimuro, S; Whitley, R J (1990) Expression of HSV-1 glycoproteins in tunicamycin-treated monkey kidney cells. Biochem Biophys Res Commun 167:1139-45
Chatterjee, S; Koga, J; Whitley, R J (1989) A role for herpes simplex virus type 1 glycoprotein E in induction of cell fusion. J Gen Virol 70 ( Pt 8):2157-62
Chatterjee, S; Whitley, R J (1989) Effect of recombinant hybrid human interferon on replication and morphogenesis of HSV-1 in monkey cells. Virus Res 12:33-41
Metcalf, J F; Chatterjee, S; Koga, J et al. (1988) Protection against herpetic ocular disease by immunotherapy with monoclonal antibodies to herpes simplex virus glycoproteins. Intervirology 29:39-49