Abstract

HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues.

Read more at nature…

 

Credit: NIAID

Download

CITATION:     1 Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain. 2 Pathology Department, Hospital Universitari Vall d’Hebron, UAB, Barcelona, Spain. 3 Pathology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. 4 Pathology Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona, Barcelona, Spain. 5 Flow Cytometry Facility, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Spain. 6AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. 7 Obstetrics and Gynecology Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona, Barcelona, Spain. 8Department of Obstetrics and Gynecology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. 9Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 10These authors contributed equally: Jon Cantero-Pérez, Judith Grau-Expósito. *email: mariajose.buzon@vhir.org; meritxell.  genesca@vhir.org        NATURE COMMUNICATIONS | (2019) 10:4739 |    ttps://doi.org/10.1038/s41467-019-12732-2 | www.nature.com/naturecommunications