Publications by authors named "Antonio Astorga-Gamaza"

4 Publications

  • Page 1 of 1

Peripheral and lung resident memory T cell responses against SARS-CoV-2.

Nat Commun 2021 05 21;12(1):3010. Epub 2021 May 21.

Infectious Diseases Department, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

Resident memory T cells (T) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, T are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7 T cells secreting IL-10. In convalescent patients, lung-T are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting T cells as important for future protection against SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23333-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140108PMC
May 2021

The active human immunodeficiency virus reservoir during antiretroviral therapy: emerging players in viral persistence.

Curr Opin HIV AIDS 2021 Jul;16(4):193-199

Infectious Disease Department, Hospital Universitari Valld'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.

Purpose Of Review: To discuss the role of CD4+ T cells with active Human immunodeficiency virus (HIV), meaning infected cells with transcriptional and/or translational viral activity during antiretroviral therapy (ART), focusing on new technologies for its detection, potential cell markers for its characterization, and evidences on the contribution of the active HIV reservoir to long-term viral persistence.

Recent Findings: HIV-infected cells expressing viral ribonucleic acid are systematically detected in subjects on long-term ART. In recent years, powerful new tools have provided significant insights into the nature, quantification, and identification of cells with active HIV, including the identification of new cell markers, and the presence of viral activity in specific cell populations located in different cellular and anatomical compartments. Moreover, studies on viral sequence integrity have identified cell clones with intact viral genomes and active viral transcription that could potentially persist for years. Together, new investigations support the notion that the active reservoir could represent a relevant fraction of long-term infected cells, and therefore, the study of its cell sources and mechanisms of maintenance could represent a significant advance in our understanding of viral persistence and the development of new curative strategies.

Summary: The presence of HIV-infected cells with viral expression during ART has been traditionally overlooked for years. Based on recent investigations, this active viral reservoir could play an important role in HIV persistence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/COH.0000000000000685DOI Listing
July 2021

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

Nat Commun 2019 10 18;10(1):4739. Epub 2019 Oct 18.

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.

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 CD4T 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 CD4T expressing CD32. Cervical explant models show that CD4T 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 CD4T 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12732-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802119PMC
October 2019

Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab.

Nat Commun 2019 08 16;10(1):3705. Epub 2019 Aug 16.

Infectious Disease Department, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-11556-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697690PMC
August 2019
-->