Isolation of HIV from saliva is a rare event, and the oral cavity does not appear to be a route for viral transmission. We have described a salivary factor that agglutinates HIV, forming large complexes. We have recently identified a second salivary activity that decreases HIV infectivity in the absence of filtration. Our hypothesis is that the salivary factors act as a natural host-defense mechanism to clear virus in infected individuals, and as a barrier to infection in uninfected individuals. The salivary factors help to remove HIV form oral secretions and virus is therefore not available for transmission or infection via the oral route. In this application we propose to further characterize the nature of the agglutinating and """"""""prefiltration"""""""" salivary HIV inhibitors, to study their mechanism of action, and to correlate the presence of cell free and cell associated HIV with levels of inhibitory activity in saliva obtained from HIV seropositive individuals. Once the salivary HIV inhibitors are identified, the mechanism of action in vitro, and the possible in vivo significance will be assessed. It is clear from our studies that there is a selective interaction between a salivary factor and HIV, but the importance of this reaction remains to be demonstrated. The possible role of salivary anti-HIV factors in vivo will be studied by correlating activity with the presence of HIV in seropositive individuals, and also with the stage of the disease. If a specific anti-HIV factor is purified from saliva, one will have opened up a potential new avenue for therapeutic drug design based upon a naturally produced anti-viral substance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE009569-07
Application #
2130630
Study Section
AIDS and Related Research Study Section 4 (ARRD)
Project Start
1990-06-04
Project End
1998-08-14
Budget Start
1996-08-15
Budget End
1998-08-14
Support Year
7
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hodinka, R L; Nagashunmugam, T; Malamud, D (1998) Detection of human immunodeficiency virus antibodies in oral fluids. Clin Diagn Lab Immunol 5:419-26
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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