Herpes simplex virus type 2 is a common sexually transmitted disease with an estimated incidence of 500,000 new cases/year. The recurrent genital lesions are physically debilitating and cause intolerable mental and social anguish. Secondary complications include elevated abortion rates, increases in the incidence of fetal malformations, and severe herpetic infections of newborn infants. Public interest supports the development of preventive therapy for HSV-2 infections. However, effective means for the prevention/cure of herpetic recurrences cannot be developed until we achieve a basic understanding of the role played by virus specific immunity in primary and recurrent cutaneous disease, ganglionic latency and reinfection. Our goal is to develop a better understanding of the immunobiology of HSV infections, including the identification of viral proteins that play key regulatory functions in cutaneous infection/reinfection, recurrent disease and ganglionic latency. Vaccinia recombinants containing the HSV glycoprotein genes gD, gB, gC, their achorless versions (glycoprotein lacks the transmembrane anchor) and multiple combinations of these 3 genes will be studied. The expression of these genes in various cell species will be determined by immunoprecipitation of cell extracts labeled with 35S-methionine, 3H-glucosamine or 3H-mannose and immunoflourescent staining of live cells with panels of monoclonal antibodies that recognize different antigenic domains on the appropriate glycoproteins. The recombinants will be studied for their ability to protect from primary and recurrent HSV-2 or HSV-1 cutaneous disease, ganglionic infection and fatal challenge. The findings will be corelated with the ability of the recombinants to induce HSV specific immunity including: (i) varus specific antibody (neutralizing, cytolytic, mediating cellular cytotoxicity) and lymphoproliferation, (ii) fine specificity of HSV specific immunoglobulins, (iii) adoptive protection against HSV challenge and phenotype of transferred cells and (iv) virus-specific cytotoxic T lymphocytes (Tc): regulatory (suppressor) functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI022192-05
Application #
3133025
Study Section
Virology Study Section (VR)
Project Start
1984-08-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Miura, S; Kulka, M; Smith, C C et al. (1994) Cutaneous ultraviolet radiation inhibits herpes simplex virus-induced lymphoproliferation in latently infected subjects. Clin Immunol Immunopathol 72:62-9
Miura, S; Burnett, J W; Aurelian, L (1993) Immunity to jellyfish venoms: suppression of venom-induced immune responses in ultraviolet B-irradiated mice. Toxicon 31:1415-22
Miura, S; Smith, C C; Burnett, J W et al. (1992) Detection of viral DNA within skin of healed recurrent herpes simplex infection and erythema multiforme lesions. J Invest Dermatol 98:68-72
Aurelian, L; Smith, C C; Wachsman, M et al. (1991) Immune responses to herpes simplex virus in guinea pigs (footpad model) and mice immunized with vaccinia virus recombinants containing herpes simplex virus glycoprotein D. Rev Infect Dis 13 Suppl 11:S924-34
Wachsman, M; Aurelian, L; Burnett, J W (1991) Human immunosuppression induced by sea nettle (Chrysaora quinquecirrha) venom. Toxicon 29:386-90
Dankert, J R (1991) Resistance of Escherichia coli to osmotically introduced complement component C9. Infect Immun 59:109-13
Dankert, J R (1989) Complement-mediated inhibition of function in complement-resistant Escherichia coli. J Immunol 142:1591-5
Wachsman, M; Aurelian, L; Smith, C C et al. (1989) Regulation of expression of herpes simplex virus (HSV) glycoprotein D in vaccinia recombinants affects their ability to protect from cutaneous HSV-2 disease. J Infect Dis 159:625-34
Aurelian, L; Yasumoto, S; Smith, C C (1988) Antigen-specific immune-suppressor factor in herpes simplex virus type 2 infections of UV B-irradiated mice. J Virol 62:2520-4
Wachsman, M; Aurelian, L; Hunter, J C et al. (1988) Expression of herpes simplex virus glycoprotein D on antigen presenting cells infected with vaccinia recombinants and protective immunity. Biosci Rep 8:323-34

Showing the most recent 10 out of 18 publications