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

Autor: Cantero, Jon, Grau-Expósito, Judith, Serra-Peinado, Carla, Rosero, D. A., Luque-Ballesteros, Laura, Astorga-Gamaza, Antonio, Castellvi, Josep., Sanhueza, T., Tapia Melendo, Gustavo, Lloveras, B., Fernández, Marco A., Prado, Julia G., Solé-Sedeno, J. M., Tarrats, A., Lecumberri, Carla, Mañalich-Barrachina, L., Centeno-Mediavilla, C., Falcó, Vicenç, Buzón, Maria José, Genescà Ferrer, Meritxell., Universitat Autònoma de Barcelona
Přispěvatelé: [Cantero-Pérez J, Grau-Expósito J, Serra-Peinado C, Rosero DA, Luque-Ballesteros L, Astorga-Gamaza A, Falcó V, Buzon MJ, Genescà M] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Malalties Infeccioses, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Mañalich-Barrachina L, Centeno-Mediavilla C] Servei de Ginecologia i Obstetrícia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
CD32
Human immunodeficiency virus (HIV)
Urogenital System::Genitalia::Genitalia
Female::Uterus::Cervix Uteri [ANATOMY]

General Physics and Astronomy
HIV Infections
Cervix Uteri
medicine.disease_cause
Pathogenesis
0302 clinical medicine
Coll uterí
sistema urogenital::genitales::genitales femeninos::útero::cuello del útero [ANATOMÍA]
Dna viral
lcsh:Science
Multidisciplinary
biology
virus diseases
Middle Aged
Viral Load
Phenotype
3. Good health
Cèl·lules T
Anti-Retroviral Agents
Female
HIV infections
Adult
Female circumcision
Science
Article
General Biochemistry
Genetics and Molecular Biology

Viral reservoirs
03 medical and health sciences
enfermedades del sistema inmune::síndromes de inmunodeficiencia::infecciones por VIH [ENFERMEDADES]
VIH (Virus)
medicine
Humans
Mucosa cervical
Aged
Disease Reservoirs
Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY]

Mucous Membrane
Cluster of differentiation
RNA
General Chemistry
Virology
Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES]
sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos [ANATOMÍA]
030104 developmental biology
HIV-1
biology.protein
Infeccions per VIH
lcsh:Q
Immunologic Memory
030217 neurology & neurosurgery
Zdroj: Nature Communications
r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol
instname
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Nature Communications, Vol 10, Iss 1, Pp 1-16 (2019)
Scientia
ISSN: 2041-1723
DOI: 10.1038/s41467-019-12732-2
Popis: 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.
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.
Databáze: OpenAIRE