Epidemiologic evidence indicates that transmission of HIV by the oral route occurs infrequently, if at all. Laboratory studies by others, and our own preliminary results presented in this proposal, have detected a factor in saliva which inhibits HIV infectivity. The factor(s) appears to be protein, are present in highest concentration in submandibular saliva, and result in a loss of viral infectivity in vitro. In this reaction, two salivary proteins (MW 32,000 and 35,000 daltons) appear to become associated with HIV aggregates.
The aims of the present study are to characterize the interaction between the salivary factor and HIV and to purify the protein from normal human submandibular saliva. Antibody or oligomer probes would be generated and used to screen a submandibular gland cDNA library to identify clones expressing the recombinant protein. The purified salivary protein, or the recombinant molecule, would then be used to study the mechanism of interaction with HIV protein(s). Finally, the level of anti-HIV activity in saliva of normal individuals and subjects with xerostomia will be evaluated to determine if decreased salivary flow is associated with a decreased amount of anti-HIV activity. These studies would provide the basis for understanding the role of saliva in modulating HIV transmission. Subsequent studies would investigate the HIV seropositive and AIDS populations to determine if the activity is altered after virus infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009569-02
Application #
3223355
Study Section
Special Emphasis Panel (SRC (08))
Project Start
1990-06-04
Project End
1993-06-03
Budget Start
1991-06-04
Budget End
1992-06-03
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Kennedy, S; Davis, C; Abrams, W R et al. (1998) Submandibular salivary proteases: lack of a role in anti-HIV activity. J Dent Res 77:1515-9
Nagashunmugam, T; Malamud, D; Davis, C et al. (1998) Human submandibular saliva inhibits human immunodeficiency virus type 1 infection by displacing envelope glycoprotein gp120 from the virus. J Infect Dis 178:1635-41
Taichman, N S; Cruchley, A T; Fletcher, L M et al. (1998) Vascular endothelial growth factor in normal human salivary glands and saliva: a possible role in the maintenance of mucosal homeostasis. Lab Invest 78:869-75
Malamud, D; Nagashunmugam, T; Davis, C et al. (1997) Inhibition of HIV infectivity by human saliva. Oral Dis 3 Suppl 1:S58-63
Nagashunmugam, T; Friedman, H M; Davis, C et al. (1997) Human submandibular saliva specifically inhibits HIV type 1. AIDS Res Hum Retroviruses 13:371-6
Nagashunmugam, T; Friedman, H M (1996) Cell-free HIV-1Zr6 vif mutants are defective in binding to peripheral blood mononuclear cells and in internalization. DNA Cell Biol 15:353-61
Chehimi, J; Ma, X; Chouaib, S et al. (1996) Differential production of interleukin 10 during human immunodeficiency virus infection. AIDS Res Hum Retroviruses 12:1141-9
Pearce-Pratt, R; Malamud, D; Phillips, D M (1994) Role of the cytoskeleton in cell-to-cell transmission of human immunodeficiency virus. J Virol 68:2898-905
Malamud, D; Friedman, H M (1993) HIV in the oral cavity: virus, viral inhibitory activity, and antiviral antibodies: a review. Crit Rev Oral Biol Med 4:461-6

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