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 Pathogjournal_title
PLoS pathogensauthors
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 NRdoi
10.1371/journal.ppat.1006163subject
Has Abstractpub_date
2017-02-16 00:00:00pages
e1006163issue
2eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-16-02365journal_volume
13pub_type
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