title: Postintegration HIV-1 infection of cervical epithelial cells mediates contact-dependent productive infection of T cells.
abstract: The female genital epithelium plays a protective role against invading pathogens; however, sexual transmission of human immunodeficiency virus type 1 (HIV-1) still occurs in healthy women. To model virus-cell interactions in this barrier during sexual transmission, we studied the uptake and infection of ectocervical and endocervical cell lines with cell-free fluorescent protein-expressing recombinant HIV-1 carrying primary transmitted/founder envelope genes. We observed that a subset of both the ectocervical and endocervical epithelial cells become productively infected with cell-free HIV-1 in a CD4-independent manner. In addition, the ability of the semen-derived enhancer of virus infection (SEVI) to enhance virus-epithelial cell interactions was studied. This infection is increased approximately 2-5 fold when inoculation occurs in the presence of SEVI fibrils. Once infected, the epithelial cells are capable of transmitting the virus to target CD4 T cells in coculture in a contact-dependent manner that uses conventional CD4- and coreceptor-dependent entry. The infection of target CD4 T cells only occurs when de novo HIV-1 is produced within the epithelial cells. These findings suggest that a subset of cervical epithelial cells may be actively involved in establishing a systemic HIV infection and should be a target when designing prevention strategies to protect against HIV-1 sexual transmission.
authors.affiliation: Department of Medicine and Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Micsenyi
authors.forename: Chati
authors.initials: C
authors.lastname: Zony
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Alvarez
authors.forename: Natasha D
authors.initials: ND
authors.lastname: Durham
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology / Q000821:virology*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D053586:Virus Internalization
chemical_list: D012367:RNA, Viral
keywords: SEVI; cervical epithelium infection; coculture; transmitted and founder HIV envelope
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