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PLoS Pathog. 2017 Feb 16;13(2):e1006163. doi: 10.1371/journal.ppat.1006163. eCollection 2017 Feb.

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

Author information

1
Gladstone Institute of Virology and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.
2
Department of Urology, University of California, San Francisco, San Francisco, CA, United States of America.
3
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United States of America.
4
Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany.
5
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
6
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
7
Center for AIDS Research, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
8
Department of Medicine, Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, United States of America.
9
Department of Medicine, Division of Gastroenterology, San Francisco General Hospital and University of California, San Francisco, San Francisco, CA, United States of America.
10
Departments of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA United States of America.
11
Aarhus Research Centre for Innate Immunology, Aarhus University, Aarhus, Denmark.
12
Departments of Medicine, Microbiology, and Immunology, University of California, San Francisco, San Francisco, CA, United States of America.

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.

PMID:
28207890
PMCID:
PMC5312882
DOI:
10.1371/journal.ppat.1006163
[Indexed for MEDLINE]
Free PMC Article

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