Anti-HIV Activity in Cervical-Vaginal Secretions from HIV-Positive and -Negative Women Correlate with Innate Antimicrobial Levels and IgG Antibodies

Ghosh, Mimi; Fahey, John V.; Shen, Zheng; Lahey, Timothy; Cu-Uvin, Susan; Wu, Zhijin; Mayer, Kenneth; Wright, Peter F.; Kappes, John C.; Ochsenbauer, Christina; Wira, Charles R.

doi:10.1371/journal.pone.0011366

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Anti-HIV Activity in Cervical-Vaginal Secretions from HIV-Positive and -Negative Women Correlate with Innate Antimicrobial Levels and IgG Antibodies

Published Date:

Jun 29 2010

Publisher's site:

http://dx.doi.org/10.1371/journal.pone.0011366 New Site Icon

Source:

PLoS One. 5(6).

[PDF-325.87 KB]

Details:

Personal Authors:

Ghosh, Mimi ; Fahey, John V. ; Shen, Zheng ; Lahey, Timothy ; Cu-Uvin, Susan ; ... More ▼

Keywords:

[+]

Pubmed ID:

20614007

Pubmed Central ID:

PMC2894072

Description:

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.

Document Type:

Journal Article

Collection(s):

Emerging Infectious Diseases
CDC Public Access

Funding:

Supporting Files:

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