Biology subjects

Burgos, J.

Publications and source records attributed to Burgos, J..

4 recordsLinked to original sources

bioRxiv2026

Site-Specific Entry Factors Define Cellular Susceptibility to SARS-CoV-2 in Human Tissues

SARS-CoV-2 primarily infects the respiratory epithelium through entry factors ACE2 and TMPRSS2. However, alternative viral entry receptors and/or modulators of viral entry factors expression may contribute to infection in respiratory as well as non-respiratory tissues, including the kidneys and colon. Using single-cell analyses, we identified novel candidates for spike-mediated viral entry in epithelial cells from diverse fresh human tissues exposed to a labeled spike-pseudotyped virus. Systematic viral tracking revealed tissue-specific membrane receptors that contribute to viral entry, functionally validated in human tissues and partially predicted by molecular modeling. We found ADAM17 and IL1R1, together with canonical molecules, to significantly facilitate viral entry in the lung parenchyma, while entry into the renal cortex was less dependable on canonical factors, but strongly modulated by JAK1/2 engagement. These findings uncover distinct viral entry mechanisms across tissues and suggest novel organ-specific therapeutic targets for patients at risk.

microbiology↗

bioRxiv2025

Induction of Resident Memory CD8+T cell Phenotypes to Eliminate the HIV reservoir

During analytical treatment interruption (ATI), failure to contain tissue HIV reservoirs remains a major barrier to remission. We conditioned peripheral blood mononuclear cells with cues that promote tissue-resident memory differentiation, aiming to reprogram HIV-specific CD8+T cells for these tissue microenvironments. Sequential IL-15/TGF-{beta}1-stimulation expanded proliferative CD103+CD39+ effector populations and restored polyfunctional HIV-specific CD8+T cell responses, irrespective of CD39 or PD-1 expression. Cytokine-stimulated CD8+T cells enhanced ex vivo elimination of the HIV reservoir, and within the induced effector pool, only CD69+ subsets expressing CD103+ or CD39+ eliminated intact HIV-1 genomes. Single-cell transcriptomics showed that IL-15/TGF-{beta}1 stimulation increased clonotypic diversity and expanded resident-like effector clusters with reduced immune-checkpoint receptor expression and augmented mitochondrial function, findings confirmed by flow cytometry. Engrafted recipients from a humanized mouse ATI model more effectively eliminated HIV+-reactivated cells after adoptive transfer of sequentially-treated CD8+T cells. Thus, IL-15/TGF-{beta}1-mediated CD8+T cell reprogramming represents a promising immunotherapy to enable immune control after ATI.

immunology↗

bioRxiv2022

Identification of HIV-Reservoir Cells with Reduced Susceptibility to Antibody-Dependent Immune Response

HIV establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fc{gamma} receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy, but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

immunology↗

bioRxiv2020

System Dynamics Modeling Of Within-Host Viral Kinetics Of Coronavirus (SARS CoV-2)

Mathematical models are being used extensively in the study of SARS-CoV-2 transmission dynamics, becoming an essential tool for decision making concerning disease control. It is now required to understand the mechanisms involved in the interaction between the virus and the immune response effector cells, both innate and adaptive, in order to support lines of research related to the use of drugs, production of protective antibodies and of course, vaccines against SARS-CoV-2. The present study, using a system dynamic approach, hypothesizes over the conditions that characterize the fraction of the population which get infected by SARS-CoV-2 as the asymptomatic patients, the mild symptomatic, acute symptomatic, and also super-spreaders, in terms of innate immune response, the initial virus load, the virus burden with shedding events, and the cytokine levels.

systems biology↗