Abstract

Infections caused by herpes simplex virus type 1 (HSV-1), and the related viral serotype HSV-2, are among the most common human infections. The severity of the infections can range from inapparent to severe keratitis or encephalitis. The HSV-1 genome has been reported to encode as many as 50 proteins. Of the viral proteins, at least four have been identified as glycoproteins. These are designated gB, gC, gD, and gE. These glycoproteins are found in virion envelopes and in the plasma membranes of infected cells. Biochemical and genetic evidence has linked gB both to penetration and to cell fusion induced by syn mutants of HSV-1. However, neither the penetration nor the cell fusion process, which both involve membrane fusion, is understood. Glycoprotein gC is not essential for virus growth in tissue culture. A number of gC- mutants have been used to investigate the requirements for membrane anchoring of this glycoprotein, which are still not completely understood. Virtually nothing is known about the incorporation of viral glycoproteins into the envelopes of virions budding through the inner nuclear membrane. It would be desirable to relate the functions of the glycoproteins to their structures. DNA sequencing studies have shown that gB, gC, and gD contain a number of identifiable structural features: amino-terminal signal peptides, large external domains, hydrophobic transmembrane sequences and charged cytoplasmic domains. The involvement of these domains in gB and gC function will be evaluated by the construction of modified glycoprotein genes in which these domains have been altered, deleted, or replaced. Recombinant viruses will be produced to express these genes, using appropriate HSV-1 mutants as vectors. The specific functions to be assessed include membrane anchoring, virion production, incorporation of glycoproteins into virions, virion penetration, cell fusion, glycoprotein processing, and transport of glycoproteins to the plasma membrane.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022162-02
Application #
3132935
Study Section
Experimental Virology Study Section (EVR)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202