Publications by authors named "Bibiana Planas"

5 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.
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http://dx.doi.org/10.1038/s41467-021-23333-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140108PMC
May 2021

Lipidomics Reveals Reduced Inflammatory Lipid Species and Storage Lipids after Switching from EFV/FTC/TDF to RPV/FTC/TDF: A Randomized Open-Label Trial.

J Clin Med 2020 Apr 25;9(5). Epub 2020 Apr 25.

Internal Medicine Department. Complexo Hospitalario Universitario de Vigo; IIS Galicia Sur, 36312 Vigo, Spain.

HIV and antiretroviral therapy affect lipid metabolism. Lipidomics quantifies several individual species that are overlooked using conventional biochemical analyses, outperforming traditional risk equations. We aimed to compare the plasma lipidomic profile of HIV patients taking efavirenz (EFV) or rilpivirine (RPV). Patients ≥ 18 years old on EFV co-formulated with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) with HIV-RNA < 50 copies/mL for ≥6 months were randomized to continue EFV/FTC/TDF (n = 14) or switch to RPV/FTC/TDF (n =15). Lipidomic analyses conducted by mass spectrometry (MS) were performed at baseline and after 12 and 24 weeks. OWLiver Care and OWLiver tests were performed to estimate the presence of fatty liver disease (NAFLD). No significant differences (83% male, median age 44 years, 6 years receiving EFV/FTC/TDF, CD4 count 740 cells/mm, TC 207 [57 HDL-C/133 LDL-C] mg/dL, TG 117 mg/dL) were observed between the groups at baseline. Significant reductions in plasma lipids and lipoproteins but increased circulating bilirubin concentrations were observed in patients who switched to RPV/FTC/TDF. Patients on RPV/FTC/TDF showed a decrease in the global amount of storage lipids (-0.137 log [fold-change] EFV vs. 0.059 log [fold-change] RPV) but an increase in lysophosphatidylcholines (LPCs) and total steroids. Compared with EFV, RPV increased metabolites with anti-inflammatory properties and reduced the repository of specific lipotoxic lipids.
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http://dx.doi.org/10.3390/jcm9051246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288166PMC
April 2020

Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations.

PLoS Pathog 2019 08 19;15(8):e1007991. Epub 2019 Aug 19.

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

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.
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http://dx.doi.org/10.1371/journal.ppat.1007991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715238PMC
August 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.
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http://dx.doi.org/10.1038/s41467-019-11556-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697690PMC
August 2019

A Novel Single-Cell FISH-Flow Assay Identifies Effector Memory CD4 T cells as a Major Niche for HIV-1 Transcription in HIV-Infected Patients.

mBio 2017 07 11;8(4). Epub 2017 Jul 11.

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

Cells that actively transcribe HIV-1 have been defined as the "active viral reservoir" in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4 T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4 T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4 T cell count and the CD4/CD8 ratio. We also found that after infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation. Persons infected with HIV-1 contain several cellular viral reservoirs that preclude the complete eradication of the viral infection. Using a novel methodology, we identified effector memory CD4 T cells, immune cells preferentially located in inflamed tissues with potent activity against pathogens, as the main cells encompassing the transcriptionally active HIV-1 reservoir in patients on antiretroviral therapy. Importantly, the identification of such cells provides us with an important target for new therapies designed to target the hidden virus and thus to eliminate the virus from the human body. In addition, because of its ability to identify cells forming part of the viral reservoir, the assay used in this study represents an important new tool in the field of HIV pathogenesis and viral persistence.
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http://dx.doi.org/10.1128/mBio.00876-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513707PMC
July 2017
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