Inhibitory function of secretory leukocyte proteinase inhibitor (SLPI) in human saliva is HIV-1 specific and varies with virus tropism.
OBJECTIVE
Secretory leukocyte proteinase inhibitor (SLPI) is an endogenous mucosa associated protein that has been proposed to possess anti-human immunodeficiency virus type 1 (HIV-1) activity. The aim of this study was to investigate the biological function of SLPI in salivary mediated inhibition of HIV infection and in addition the inhibitory effect of SLPI using isolates of varied virus tropism.


METHODS
The inhibitory effect of HIV-1 infection in vitro, mediated by 60 different saliva samples was analyzed with respect to levels of SLPI. Salivary samples depleted from IgA and SLPI, respectively, were further analyzed for anti-HIV activity. The antiviral effect of recombinant SLPI was investigated within an in vitro system of HIV-1 infection of target cells using a panel of viral isolates with distinct coreceptor usage. Furthermore we tested a panel of overlapping synthetic peptides, representing the amino acids in SLPI, for their capacity to inhibit HIV-1 infection of human peripheral blood mononuclear cells (PBMCs).


CONCLUSIONS
These experiments show that elevated levels of salivary SLPI can be associated with an increased inhibitory effect of the whole saliva sample, and that this inhibitory effect is decreased with broad coreceptor usage of the virus.
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden. pia.skott@mtc.ki.se
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Skott
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Lucht
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Ehnlund
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Björling
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000821:virology; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000821:virology; D016014:Linear Models; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D011994:Recombinant Proteins; D012463:Saliva / Q000737:chemistry / Q000502:physiology* / Q000821:virology; D012471:Salivary Proteins and Peptides / Q000032:analysis / Q000502:physiology*; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D018709:Statistics, Nonparametric; D014774:Virulence
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D007071:Immunoglobulin A, Secretory; D008565:Membrane Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D012471:Salivary Proteins and Peptides; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors