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

被引：86

作者：

Cantero-Perez, Jon ^{[1
]}

Grau-Exposito, Judith ^{[1
]}

Serra-Peinado, Carla ^{[1
]}

Rosero, Daniela A. ^{[1
]}

Luque-Ballesteros, Laura ^{[1
]}

Astorga-Gamaza, Antonio ^{[1
]}

Castellvi, Josep ^{[2
]}

Sanhueza, Tamara ^{[3
]}

Tapia, Gustavo ^{[3
]}

Lloveras, Belen ^{[4
]}

Fernandez, Marco A. ^{[5
]}

Prado, Julia G. ^{[6
]}

Sole-Sedeno, Josep M. ^{[7
]}

Tarrats, Antoni ^{[8
]}

Lecumberri, Carla ^{[8
]}

Manalich-Barrachina, Laura ^{[9
]}

Centeno-Mediavilla, Cristina ^{[9
]}

Falco, Vicenc ^{[1
]}

Buzon, Maria J. ^{[1
]}

Genesca, Meritxell ^{[1
]}

机构：

[1] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Inst Recerca VHIR, Infect Dis Dept, Barcelona, Spain

[2] UAB, Hosp Univ Vall dHebron, Pathol Dept, Barcelona, Spain

[3] Hosp Badalona Germans Trias & Pujol, Pathol Dept, Barcelona, Spain

[4] Univ Autonoma Barcelona, Hosp Mar, Pathol Dept, Parc Salut Mar, Barcelona, Spain

[5] Inst Invest Ciencies Salut Germans Trias & Pujol, Flow Cytometry Facil, Badalona, Spain

[6] Univ Autonoma Barcelona, Inst Invest Ciencies Salut Germans Trias & Pujol, AIDS Res Inst IrsiCaixa, Badalona, Spain

[7] Univ Autonoma Barcelona, Hosp Mar, Parc Salut Mar, Obstet & Gynecol Dept, Barcelona, Spain

[8] Hosp Badalona Germans Trias & Pujol, Dept Obstet & Gynecol, Barcelona, Spain

[9] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Dept Obstet & Gynecol, Barcelona, Spain

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

SEXUAL TRANSMISSION; LATENT RESERVOIR; TISSUE; REPLICATION; INFECTION; BLOOD; EXPRESSION; SIV; PERSISTENCE; PHENOTYPE;

D O I：

10.1038/s41467-019-12732-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 TRM 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.

引用

页数：16

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