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

HIV viral reservoirs are established very early during infection. Resident memory T cells (T RM ) 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 +...

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Published in:	Nature communications Vol. 10; no. 1; pp. 4739 - 16
Main Authors:	Cantero-Pérez, Jon, Grau-Expósito, Judith, Serra-Peinado, Carla, Rosero, Daniela A., Luque-Ballesteros, Laura, Astorga-Gamaza, Antonio, Castellví, Josep, Sanhueza, Tamara, Tapia, Gustavo, Lloveras, Belen, Fernández, Marco A., Prado, Julia G., Solé-Sedeno, Josep M., Tarrats, Antoni, Lecumberri, Carla, Mañalich-Barrachina, Laura, Centeno-Mediavilla, Cristina, Falcó, Vicenç, Buzon, Maria J., Genescà, Meritxell
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 18-10-2019 Nature Publishing Group Nature Portfolio
Subjects:	13/106 13/31 13/51 14/32 38/77 631/250/255/1901 631/326/596/2564 692/699/255/1901 Adult Aged Anti-Retroviral Agents - therapeutic use Antiretroviral drugs Antiretroviral therapy CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - virology Cervix Uteri - drug effects Cervix Uteri - virology Deoxyribonucleic acid Disease Reservoirs - virology DNA Female Genital tract HIV HIV Infections - drug therapy HIV Infections - immunology HIV Infections - virology HIV-1 - drug effects HIV-1 - genetics HIV-1 - immunology Human immunodeficiency virus Humanities and Social Sciences Humans Immunologic Memory - immunology Immunological memory Infections Lymphocytes Lymphocytes T Memory cells Middle Aged Mucosa Mucous Membrane - drug effects Mucous Membrane - virology multidisciplinary Pathogenesis Phenotypes Proteins Ribonucleic acid RNA Science Science (multidisciplinary) Tissues Viral Load - drug effects Viral Load - genetics Viral Load - immunology
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Summary:	HIV viral reservoirs are established very early during infection. Resident memory T cells (T RM ) 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 + T RM 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 + T RM expressing CD32. Cervical explant models show that CD4 + T RM preferentially support HIV infection and harbor more viral DNA and protein than non-T RM . Importantly, cervical tissue from ART-suppressed HIV + women contain high levels of viral DNA and RNA, being the T RM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4 + T RM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider T RM phenotypes, which are widely distributed in tissues. Using cervical explant models and cervical tissue from ART-suppressed HIV + women, the authors here show that resident memory T cells (T RM ) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-T RM , suggesting that T RM may serve as viral reservoir in the cervical mucosa.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-019-12732-2