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 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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| Abstract | 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. |
|---|---|
| AbstractList | Using cervical explant models and cervical tissue from ART-suppressed HIV+ women, the authors here show that resident memory T cells (TRM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-TRM, suggesting that TRM may serve as viral reservoir in the cervical mucosa. Abstract 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. 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. HIV viral reservoirs are established very early during infection. Resident memory T cells (T ) 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 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 expressing CD32. Cervical explant models show that CD4 T preferentially support HIV infection and harbor more viral DNA and protein than non-T . Importantly, cervical tissue from ART-suppressed HIV women contain high levels of viral DNA and RNA, being the T fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4 T as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider T phenotypes, which are widely distributed in tissues. 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. |
| ArticleNumber | 4739 |
| Author | Luque-Ballesteros, Laura Serra-Peinado, Carla Centeno-Mediavilla, Cristina Buzon, Maria J. Astorga-Gamaza, Antonio Tapia, Gustavo Rosero, Daniela A. Sanhueza, Tamara Prado, Julia G. Solé-Sedeno, Josep M. Mañalich-Barrachina, Laura Cantero-Pérez, Jon Falcó, Vicenç Genescà, Meritxell Lloveras, Belen Fernández, Marco A. Lecumberri, Carla Grau-Expósito, Judith Castellví, Josep Tarrats, Antoni |
| Author_xml | – sequence: 1 givenname: Jon orcidid: 0000-0003-4844-6143 surname: Cantero-Pérez fullname: Cantero-Pérez, Jon organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 2 givenname: Judith orcidid: 0000-0001-9350-2429 surname: Grau-Expósito fullname: Grau-Expósito, Judith organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 3 givenname: Carla orcidid: 0000-0003-1413-3990 surname: Serra-Peinado fullname: Serra-Peinado, Carla organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 4 givenname: Daniela A. orcidid: 0000-0002-3212-2710 surname: Rosero fullname: Rosero, Daniela A. organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 5 givenname: Laura orcidid: 0000-0001-9515-5889 surname: Luque-Ballesteros fullname: Luque-Ballesteros, Laura organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 6 givenname: Antonio surname: Astorga-Gamaza fullname: Astorga-Gamaza, Antonio organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 7 givenname: Josep orcidid: 0000-0001-5745-9996 surname: Castellví fullname: Castellví, Josep organization: Pathology Department, Hospital Universitari Vall d’Hebron, UAB – sequence: 8 givenname: Tamara surname: Sanhueza fullname: Sanhueza, Tamara organization: Pathology Department, Hospital Universitari Germans Trias i Pujol, Badalona – sequence: 9 givenname: Gustavo surname: Tapia fullname: Tapia, Gustavo organization: Pathology Department, Hospital Universitari Germans Trias i Pujol, Badalona – sequence: 10 givenname: Belen surname: Lloveras fullname: Lloveras, Belen organization: Pathology Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona – sequence: 11 givenname: Marco A. orcidid: 0000-0002-3921-2209 surname: Fernández fullname: Fernández, Marco A. organization: Flow Cytometry Facility, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol – sequence: 12 givenname: Julia G. orcidid: 0000-0002-5439-4645 surname: Prado fullname: Prado, Julia G. organization: AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona – sequence: 13 givenname: Josep M. orcidid: 0000-0002-0789-6896 surname: Solé-Sedeno fullname: Solé-Sedeno, Josep M. organization: Obstetrics and Gynecology Department, Hospital del Mar, Parc de Salut Mar, Universitat Autònoma de Barcelona – sequence: 14 givenname: Antoni orcidid: 0000-0002-1276-8522 surname: Tarrats fullname: Tarrats, Antoni organization: Department of Obstetrics and Gynecology, Hospital Universitari Germans Trias i Pujol, Badalona – sequence: 15 givenname: Carla orcidid: 0000-0001-6509-5256 surname: Lecumberri fullname: Lecumberri, Carla organization: Department of Obstetrics and Gynecology, Hospital Universitari Germans Trias i Pujol, Badalona – sequence: 16 givenname: Laura surname: Mañalich-Barrachina fullname: Mañalich-Barrachina, Laura organization: Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona – sequence: 17 givenname: Cristina surname: Centeno-Mediavilla fullname: Centeno-Mediavilla, Cristina organization: Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona – sequence: 18 givenname: Vicenç orcidid: 0000-0001-9626-0023 surname: Falcó fullname: Falcó, Vicenç organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 19 givenname: Maria J. orcidid: 0000-0003-4427-9413 surname: Buzon fullname: Buzon, Maria J. email: mariajose.buzon@vhir.org organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona – sequence: 20 givenname: Meritxell orcidid: 0000-0001-6413-3812 surname: Genescà fullname: Genescà, Meritxell email: meritxell.genesca@vhir.org organization: Infectious Diseases Department, Hospital Universitari Vall d’Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona |
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| Copyright | The Author(s) 2019 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| GrantInformation_xml | – fundername: This work was primarily supported by grants from the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01235 and PI17/01470) and a fellowship award from the Dexeus foundation for women’s health research to M.G., grants R21AI118411 and SAF2015-67334-R (from the Spanish Secretariat of Science and Innovation and FEDER funds) to M.J.B and grants from the ISCIII (PI14/01058 and PI17/00164) to J.G.P. M.G, M.J.B and. J.G.P are supported by the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007) M.G. is currently supported by the “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan government, while the Miguel Servet program from the ISCIII supports M.J.B (CP17/00179) and J.G.P (CP15/00014). – fundername: Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) grantid: CP17/00179; CP15/00014 funderid: https://doi.org/10.13039/501100004587 – fundername: NIAID NIH HHS grantid: R21 AI118411 – fundername: ; – fundername: ; grantid: CP17/00179; CP15/00014 |
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| Snippet | 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... HIV viral reservoirs are established very early during infection. Resident memory T cells (T ) are present in tissues such as the lower female genital tract,... Abstract HIV viral reservoirs are established very early during infection. Resident memory T cells (T RM ) are present in tissues such as the lower female... 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,... Using cervical explant models and cervical tissue from ART-suppressed HIV+ women, the authors here show that resident memory T cells (TRM) in the cervical... |
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| Title | Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa |
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