Mucosal stromal fibroblasts markedly enhance HIV infection of CD4+ T cells.
Jason A NeidlemanJoseph C ChenNargis KohgadaiJanis A MüllerAnders LaustsenKarthiga ThavachelvamKaren S JangChristina M StürzelJennifer J JonesChristina OchsenbauerAvantika ChitreMa SomsoukMaurice M GarciaJames F SmithRuth M GreenblattJan MünchMartin R JakobsenLinda C GiudiceWarner C GreeneNadia R RoanPublished in: PLoS pathogens (2017)
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.
Keyphrases
- antiretroviral therapy
- hiv infected
- hiv positive
- human immunodeficiency virus
- hiv aids
- hiv testing
- dendritic cells
- hepatitis c virus
- men who have sex with men
- extracellular matrix
- bone marrow
- ulcerative colitis
- gene expression
- immune response
- south africa
- signaling pathway
- regulatory t cells
- big data
- artificial intelligence
- preterm birth