Biology subjects

Puertas, M. C.

Publications and source records attributed to Puertas, M. C..

3 recordsLinked to original sources

bioRxiv2026

MIF overexpression upon SARS-CoV-2 infection induces neural regeneration in human-derived brain organoids

While SARS-CoV-2 primarily targets the respiratory system, its neurological effects have become a significant clinical concern. Postmortem analyses reveal astrogliosis, neuronal death, and blood-brain barrier dysfunction, yet the interplay between neural injury and endogenous repair remains unclear. Here, we employed human embryonic stem cell-derived brain organoids to examine viral tropism, bystander effects, and regenerative responses following infection. Single-cell transcriptomics and histological assays showed that SARS-CoV-2 productively infects neurons, neural progenitors, astroglia, and choroid plexus cells, triggering widespread apoptosis and senescence in both infected and neighboring cells. Despite low infection rates, organoids activated robust regenerative programs, including axon guidance, Wnt pathway signaling in mature neurons, and radial glia proliferation. Importantly, macrophage migration inhibitory factor (MIF) emerged as a key mediator, being strongly upregulated in both infected and uninfected cells, particularly in the choroid plexus. Recombinant MIF promoted dendritic outgrowth and cortical progenitor activation in uninfected organoids. Computational analyses indicated that MIF stimulates neural regenerative via EGFR signaling and upregulates its own expression in non-infected cells. These findings identify MIF as a molecular link between SARS-CoV-2-induced neural damage and regenerative activation in cortical cells.

cell biology↗

bioRxiv2025

HIV-1 Envelope glycoprotein modulates CXCR4 clustering and dynamics on the T cell membrane

HIV-1 entry into susceptible cells requires the dynamic interaction of its envelope (Env) glycoprotein with the host cell receptor CD4 and a co-receptor, either CCR5 or CXCR4. While the core molecular mechanisms driving Env-receptor interactions and subsequent membrane fusion are well characterized, the precise nanoscale spatial reorganization of these co-receptors at the viral binding site remains poorly defined. In this study, we employed single-particle tracking total internal reflection fluorescence (SPT-TIRF) microscopy to quantitatively analyze nanoscale organizational changes of CXCR4 on the surface of CD4+ T cells following binding by X4-tropic HIV-1. Our data reveal that both recombinant X4-gp120 and virus-like particles expressing physiological levels of X4 Env proteins (gp120 and gp41) promote CXCR4 clustering, a phenomenon linked to cell infection. Furthermore, these ligands induced oligomerization of CXCR4R334X, a naturally occurring mutant associated with WHIM syndrome that supports HIV-1 infection but fails to oligomerize in response to CXCL12. Our findings establish a link between CXCR4 clustering and HIV-1 infection, enhancing our understanding of the initial events in viral attachment and entry. These results further suggest that HIV-1 depends on a specific spatial arrangement of co-receptors, distinct from that induced by their natural chemokine ligands, highlighting the critical role of cell-surface receptor spatial organization in dictating cellular function.

immunology↗

bioRxiv2021

Gut Microbiome Signatures Linked to HIV-1 Reservoir Size and Viremia Control

BackgroundThe potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. ResultsViremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways, including methanogenesis and carbohydrate biosynthesis, were significantly decreased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. ConclusionsThis proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

immunology↗