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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Neidleman JA,Chen JC,Kohgadai N,Müller JA,Laustsen A,Thavachelvam K,Jang KS,Stürzel CM,Jones JJ,Ochsenbauer C,Chitre A,Somsouk M,Garcia MM,Smith JF,Greenblatt RM,Münch J,Jakobsen MR,Giudice LC,Greene WC,Roan NR

doi

10.1371/journal.ppat.1006163

subject

Has Abstract

pub_date

2017-02-16 00:00:00

pages

e1006163

issue

2

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-02365

journal_volume

13

pub_type

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