TY - JOUR
T1 - Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa
AU - Cantero-Pérez, Jon
AU - Grau-Expósito, Judith
AU - Serra-Peinado, Carla
AU - Rosero, Daniela A.
AU - Luque-Ballesteros, Laura
AU - Astorga-Gamaza, Antonio
AU - Castellví, Josep
AU - Sanhueza, Tamara
AU - Tapia, Gustavo
AU - Lloveras, Belen
AU - Fernández, Marco A.
AU - Prado, Julia G.
AU - Solé-Sedeno, Josep M.
AU - Tarrats, Antoni
AU - Lecumberri, Carla
AU - Mañalich-Barrachina, Laura
AU - Centeno-Mediavilla, Cristina
AU - Falcó, Vicenç
AU - Buzon, Maria J.
AU - Genescà, Meritxell
PY - 2019/10/18
Y1 - 2019/10/18
N2 - © 2019, The Author(s). 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.
AB - © 2019, The Author(s). 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.
UR - http://www.mendeley.com/research/resident-memory-t-cells-cellular-reservoir-hiv-cervical-mucosa
U2 - 10.1038/s41467-019-12732-2
DO - 10.1038/s41467-019-12732-2
M3 - Article
C2 - 31628331
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
M1 - 4739
ER -