Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Jason A Neidleman, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Joseph C Chen, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Nargis Kohgadai, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Janis A Müller, Ulm University Medical Center, Institute of Molecular Virology, Meyerhofstr. 1, Ulm 89081, Germany.
  • ,
  • Anders Laustsen
  • Karthiga Thavachelvam
  • Karen S Jang, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Christina M Stürzel, Ulm University Medical Center, Institute of Molecular Virology, Meyerhofstr. 1, Ulm 89081, Germany.
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  • Jennifer Jones, Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
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  • Christina Ochsenbauer, Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
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  • Avantika Chitre, Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Ma Somsouk, Department of Medicine, Division of Gastroenterology, San Francisco General Hospital and University of California, San Francisco, San Francisco, CA, United States of America.
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  • Maurice M Garcia, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • James F Smith, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Ruth M Greenblatt, Departments of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States of America.
  • ,
  • Jan Münch, Ulm University Medical Center, Institute of Molecular Virology, Meyerhofstr. 1, Ulm 89081, Germany.
  • ,
  • Martin R Jakobsen
  • Linda C. Giudice, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Warner C Greene, Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.
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  • Nadia R Roan, Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.

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.

Original languageEnglish
JournalP L o S Pathogens
Volume13
Issue2
Pages (from-to)e1006163
ISSN1553-7366
DOIs
Publication statusPublished - Feb 2017

    Research areas

  • Journal Article

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