Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa

Jon Cantero-Pérez, Judith Grau-Expósito, Carla Serra-Peinado, Daniela A. Rosero, Laura Luque-Ballesteros, Antonio Astorga-Gamaza, Josep Castellví, Tamara Sanhueza, Gustavo Tapia, Belen Lloveras, Marco A. Fernández, Julia G. Prado, Josep M. Solé-Sedeno, Antoni Tarrats, Carla Lecumberri, Laura Mañalich-Barrachina, Cristina Centeno-Mediavilla, Vicenç Falcó, Maria J. Buzon () and Meritxell Genescà ()
Additional contact information
Jon Cantero-Pérez: Universitat Autònoma de Barcelona
Judith Grau-Expósito: Universitat Autònoma de Barcelona
Carla Serra-Peinado: Universitat Autònoma de Barcelona
Daniela A. Rosero: Universitat Autònoma de Barcelona
Laura Luque-Ballesteros: Universitat Autònoma de Barcelona
Antonio Astorga-Gamaza: Universitat Autònoma de Barcelona
Josep Castellví: Hospital Universitari Vall d’Hebron, UAB
Tamara Sanhueza: Hospital Universitari Germans Trias i Pujol, Badalona
Gustavo Tapia: Hospital Universitari Germans Trias i Pujol, Badalona
Belen Lloveras: Universitat Autònoma de Barcelona
Marco A. Fernández: Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol
Julia G. Prado: Universitat Autònoma de Barcelona
Josep M. Solé-Sedeno: Universitat Autònoma de Barcelona
Antoni Tarrats: Hospital Universitari Germans Trias i Pujol, Badalona
Carla Lecumberri: Hospital Universitari Germans Trias i Pujol, Badalona
Laura Mañalich-Barrachina: Universitat Autònoma de Barcelona
Cristina Centeno-Mediavilla: Universitat Autònoma de Barcelona
Vicenç Falcó: Universitat Autònoma de Barcelona
Maria J. Buzon: Universitat Autònoma de Barcelona
Meritxell Genescà: Universitat Autònoma de Barcelona

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12732-2

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