20614007

PMC2894072

Background

We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(−) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (−) women inhibit HIV infection.

Methodology/Principal Findings

CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(−) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+) women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(−) controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus) viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3α indicated that each was present in CVL from HIV(+) and HIV(−) women. HBD2 and MIP3α correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+) women.

Conclusions/Significance

These findings indicate that CVL from healthy HIV(+) and HIV(−) women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

CDC Public Access
Emerging Infectious Diseases

AI066884/AI/NIAID NIH HHS/United States
AI13541/AI/NIAID NIH HHS/United States
AI40350/AI/NIAID NIH HHS/United States
AI51877/AI/NIAID NIH HHS/United States
CDC 106795/PHS HHS/United States
K24 AI066884/AI/NIAID NIH HHS/United States
P01 AI051877/AI/NIAID NIH HHS/United States
P30 AI042853/AI/NIAID NIH HHS/United States
P30-AI27767/AI/NIAID NIH HHS/United States
P30AI42853/AI/NIAID NIH HHS/United States
R01 AI013541/AI/NIAID NIH HHS/United States
R01 AI071761/AI/NIAID NIH HHS/United States
R03 AI102837/AI/NIAID NIH HHS/United States
R21 AI040350/AI/NIAID NIH HHS/United States
R37 AI013541/AI/NIAID NIH HHS/United States
U01-AI067854/AI/NIAID NIH HHS/United States