Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.
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.


RESULTS
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 MIP3alpha indicated that each was present in CVL from HIV(+) and HIV(-) women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+) women.


CONCLUSIONS
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.
Ghosh
Mimi
M
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, United States of America.
Fahey
John V
JV
Shen
Zheng
Z
Lahey
Timothy
T
Cu-Uvin
Susan
S
Wu
Zhijin
Z
Mayer
Kenneth
K
Wright
Peter F
PF
Kappes
John C
JC
Ochsenbauer
Christina
C
Wira
Charles R
CR
D000328:Adult; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000032:analysis*; D014621:Vagina / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load
D007074:Immunoglobulin G