title: Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.
abstract: Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells-by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV-without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors. In comparison, mucosal epithelial cells secrete antivirals and inhibit HIV infection. These data suggest that breaches in the epithelium allow external or luminal HIV to escape an antiviral environment to access the infection-favorable environment of the stromal fibroblasts, and suggest that resident fibroblasts have a central, but previously unrecognized, role in HIV acquisition at mucosal sites. Inhibiting fibroblast-mediated enhancement of HIV infection should be considered as a novel prevention strategy.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.|Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Neidleman
authors.affiliation: Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.|Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Nargis
authors.initials: N
authors.lastname: Kohgadai
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Janis A
authors.initials: JA
authors.lastname: Müller
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Laustsen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Karthiga
authors.initials: K
authors.lastname: Thavachelvam
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.|Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Karen S
authors.identifier: 0000-0002-0000-3848
authors.initials: KS
authors.lastname: Jang
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.|Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Christina
authors.identifier: 0000-0003-1166-5879
authors.initials: C
authors.lastname: Ochsenbauer
authors.affiliation: Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Avantika
authors.identifier: 0000-0002-5505-5848
authors.initials: A
authors.lastname: Chitre
authors.affiliation: Department of Medicine, Division of Gastroenterology, San Francisco General Hospital and University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Ma
authors.initials: M
authors.lastname: Somsouk
authors.affiliation: Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Maurice M
authors.initials: MM
authors.lastname: Garcia
authors.affiliation: Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: James F
authors.initials: JF
authors.lastname: Smith
authors.affiliation: Departments of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States of America.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.|Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jakobsen
authors.affiliation: Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.|Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Warner C
authors.initials: WC
authors.lastname: Greene
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.|Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Roan
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018920:Coculture Techniques; D004717:Endometrium / Q000166:cytology / Q000821:virology; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry; D052816:Foreskin / Q000166:cytology / Q000821:virology; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000821:virology; D008297:Male; D009092:Mucous Membrane / Q000166:cytology / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D014521:Urethra / Q000166:cytology / Q000821:virology