A potent activator of HIV-1 replication is present in the genital tract of a subset of HIV-1-infected and uninfected women.
OBJECTIVE
To determine whether the female genital tract contains factors that affect HIV-1 replication. Cervicovaginal lavage (CVL) samples were collected from HIV-1-seropositive and seronegative women and added to cell cultures.


METHODS
HIV p24 production was used to measure the effects of CVL on replication of HIVMN in a T-cell line, of a primary isolate in peripheral blood mononuclear cells, or on HIV expression by the latently-infected monocytic U1 cell line. The effects of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity.


RESULTS
Increased replication of HIVMN and a primary isolate were observed in T cells cultured with CVL samples from three out of 38 HIV-infected women, one out of four uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activation of the HIV LTR. The HIV-inducing activity was highly stable to heat but was sensitive to proteases, indicating that the activity was distinct from heat-labile cytokines including tumour necrosis factor-alpha.


CONCLUSIONS
This is the first study to show that a factor which can stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially affect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.
Spear
G T
GT
Department of Immunology/Microbiology, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA.
al-Harthi
L
L
Sha
B
B
Saarloos
M N
MN
Hayden
M
M
Massad
L S
LS
Benson
C
C
Roebuck
K A
KA
Glick
N R
NR
Landay
A
A
D002478:Cells, Cultured; D010450:Endopeptidases / Q000494:pharmacology; D005260:Female; D005836:Genitalia, Female / Q000378:metabolism* / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000635:transmission / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D018023:HIV Seronegativity; D006679:HIV Seropositivity; D015497:HIV-1 / Q000254:growth & development* / Q000472:pathogenicity; D006361:Heating; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D009000:Monocytes / Q000821:virology; D013601:T-Lymphocytes / Q000821:virology; D007507:Therapeutic Irrigation; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology; D017735:Virus Latency
D016655:HIV Core Protein p24; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases