Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro.
Infection of adherent primary monocytes with HIV-1Ba-L is significantly suppressed in the presence of human saliva. By reverse transcriptase (RT) levels, saliva, although present for only 1 h during monocyte viral exposure, inhibited HIV-1 infectivity for 3 wk after infection, whereas human plasma and synovial fluid failed to inhibit HIV-1 infectivity. Antiviral activity was identified in the saliva soluble fraction, and to determine the factor(s) responsible, individual saliva proteins were examined. Of those proteins examined, only secretory leukocyte protease inhibitor (SLPI) was found to possess anti-HIV-1 activity at physiological concentrations. SLPI anti-HIV-1 activity was dose dependent, with maximal inhibition at 1-10 micrograms/ml (> 90% inhibition of RT activity). SLPI also partially inhibited HIV-1IIIB infection in proliferating human T cells. SLPI appears to target a host cell-associated molecule, since no interaction with viral proteins could be demonstrated. However, SLPI anti-HIV-1 activity was not due to direct interaction with or downregulation of the CD4 antigen. Partial depletion of SLPI in whole saliva resulted in decreased anti-HIV-1 activity of saliva. These data indicate that SLPI has antiretroviral activity and may contribute to the important antiviral activity of saliva associated with the infrequent oral transmission of HIV-1.
McNeely
T B
TB
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Dealy
M
M
Dripps
D J
DJ
Orenstein
J M
JM
Eisenberg
S P
SP
Wahl
S M
SM
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D012463:Saliva / Q000502:physiology; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000821:virology
D000998:Antiviral Agents; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors