Although HIV RNA can be detected in saliva, the difficulty in culturing HIV from oral presence of HIV inhibitors in saliva strongly suggest that saliva is not a source of infectious virus and that transmission through the oral route is, at best, inefficient. Recent studies, however, have raised doubts about this assumption. Thus, macaques may become orally infected with SIV; moreover, human seroconversion may occur under conditions where the only risk is oral-genital contact. We reported that most seronegative individuals secrete salivary proteins which specifically block the infectivity of HIV-1 in vitro. This inhibition is seen with both laboratory strains and clinical HIV isolates and is specific for HIV-1. Thus, our studies support the notion that salivary proteins exert a specific inhibitory effect on HIV-1 infection. We recently identified salivary agglutinin (SAG) as a key protein in saliva that inhibits HIV infectivity. Our hypothesis is that SAG, and perhaps other salivary proteins with anti-HIV-1 activity, are responsible for modulating HIV transmission and acquisition by the oral route. To test this hypothesis, we propose: 1. To identify the active domains of salivary agglutinin (SAG) involved in the inhibition of HIV-1 infection. 2. To examine the interaction of SAG with and to ascertain if this interaction results in shedding of gp120 from the virus. 3. To determine the mechanism by which salivary proteins inhibit HIV infectivity using in vitro models of oral infection. 4. To define the significance of anti-HIV proteins in saliva obtained from HIV-seropositive donors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012930-03
Application #
6350605
Study Section
Special Emphasis Panel (ZDE1-YS (45))
Program Officer
Mangan, Dennis F
Project Start
1999-02-01
Project End
2003-01-31
Budget Start
2001-02-01
Budget End
2003-01-31
Support Year
3
Fiscal Year
2001
Total Cost
$394,948
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Wu, Zhiwei; Van Ryk, Donald; Davis, Cheryl et al. (2003) Salivary agglutinin inhibits HIV type 1 infectivity through interaction with viral glycoprotein 120. AIDS Res Hum Retroviruses 19:201-9
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Dowd, C S; Zhang, W; Li, C et al. (2001) From receptor recognition mechanisms to bioinspired mimetic antagonists in HIV-1/cell docking. J Chromatogr B Biomed Sci Appl 753:327-35