title: 17β-Estradiol inhibits HIV-1 by inducing a complex formation between β-catenin and estrogen receptor α on the HIV promoter to suppress HIV transcription.
abstract: Human Immunodeficiency virus type 1 (HIV-1) disproportionately affects women, accounting for > 50% of new HIV infections in adults worldwide. While multiple mechanisms may contribute to a greater degree of HIV infection in women than men, we evaluated the direct effect of 17β-estradiol, the most bioactive form of estrogen in women, on HIV replication in peripheral blood mononuclear cells (PBMCs). We demonstrate that 17β-estradiol, in an ERα dependent manner, inhibits HIV replication by activating β-catenin signaling. Specifically, we show for the first time that 17β-estradiol induces a complex formation between ERα and β-catenin which tether on the HIV LTR at -143nt site from +1 start site of HIV transcription to repress HIV promoter activity. These studies define a role of 17β-estradiol in inhibiting HIV replication which may impact HIV pathogenesis in women and add to a growing list of viruses that are inhibited by 17β-estradiol through ERα engagment.
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Szotek
authors.forename: Srinivas D
authors.initials: SD
authors.lastname: Narasipura
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D000293:Adolescent; D000328:Adult; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D051176:beta Catenin; D004958:Estradiol
keywords: Estradiol; Female sex hormones; HIV; HIV LTR; Pathogenesis; Retroviruses; Transcription; Women; β-Catenin