title: Enhanced HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women correlates with increased inflammatory responses.
abstract: Knowledge about early innate immune responses at the mucosal surfaces of the female genital tract is important in understanding the pathogenesis of heterosexual transmission of human immunodeficiency virus type-1 (HIV-1). As estradiol decreases inflammatory responses, we postulated that an estradiol-deficient state such as post-menopause could enhance expression of inflammatory factors that stimulate HIV-1 replication. We compare HIV-1 integration, transcription, and viral p24 release levels among ectocervical tissues obtained from pre- and post-menopausal donors. We detected enhanced HIV-1 p24 release levels in post- compared with pre-menopausal tissues (P<0.0001), but saw no difference in HIV-1 integration. Overall, 100% of post-menopausal tissues exhibited levels of HIV-1 transcription above background compared with only 60% of pre-menopausal tissues. Increased HIV-1 transcription was associated with enhanced interleukin (IL)-1β, IL-6, monocyte chemotactic protein-1, growth-regulated oncogene-α, and interferon-γ-inducible protein-10 expression. Neutralization and nuclear factor-κB-targeting small-interfering RNA experiments both decreased HIV-1 transcription, suggesting that the early inflammatory response may facilitate HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women.
authors: Research Service, V.A. Medical Center, White River Junction, Vermont, USA.
authors: C
authors: C
authors: Rollenhagen
authors: S N
authors: SN
authors: Asin
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002828:Choristoma; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D018836:Inflammation Mediators / Q000378:metabolism; D008593:Menopause / Q000276:immunology*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D016207:Cytokines; D016655:HIV Core Protein p24; D018836:Inflammation Mediators; D016328:NF-kappa B; D034741:RNA, Small Interfering