A human immunodeficiency virus (HIV)-inducing factor from the female genital tract activates HIV-1 gene expression through the kappaB enhancer.
Virus-enhancing factors present in the female genital tract may influence the transmission of human immunodeficiency virus type 1 (HIV-1). Previously, the presence of a heat-stable soluble factor in the cervicovaginal lavage (CVL) fluid of both HIV-infected and -uninfected women that induces HIV-1 expression in T cells and monocytes was reported. Now this CVL factor was shown to increase HIV-1 gene expression through the activation of the kappaB enhancer in the viral long terminal repeat (LTR). DNA binding studies, together with functional studies using mutant LTR reporter constructs, indicate the requirement for an NF-kappaB-dependent pathway in the CVL-mediated activation of HIV-1 expression. CVL samples that activated HIV-1 expression also stimulated AP-1-dependent transcription. These data demonstrate that an HIV-inducing factor, distinct from heat-labile cytokines, present in the female genital mucosa can activate AP-1 and NF-kappaB and increase HIV-1 gene expression through the kappaB enhancer, possibly contributing to HIV-1 transmission.
Department of Immunology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA. lalharth@rush.edu
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L
Al-Harthi
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Spear
F B
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Hashemi
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A
Landay
B E
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Sha
K A
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Roebuck
D000328:Adult; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005260:Female; D015967:Gene Expression Regulation, Viral; D005836:Genitalia, Female / Q000378:metabolism / Q000821:virology*; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics*; D007507:Therapeutic Irrigation; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D016662:Virus Integration
D016328:NF-kappa B; D018808:Transcription Factor AP-1