Biology subjects

Gonzalez-Granado, L. I.

Publications and source records attributed to Gonzalez-Granado, L. I..

3 recordsLinked to original sources

bioRxiv2026

The primary and secondary immune response to Epstein-Barr virus infection of human tonsil organoids

Epstein-Barr virus (EBV) is a human herpesvirus that causes acute infectious mononucleosis (IM) and is associated with cancer and autoimmune disease. Humans are the only natural host for EBV and humanised mice are the only small animal model of infection. Consequently, although IM in adults following primary infection has been studied intensively, little is known about the virological and immunological events that occur during the initial phases of the virus-host interaction. EBV is usually transmitted via saliva exchange, and is thought to infect its main host, the human B cell, in mucosal secondary lymphoid tissues, such as the tonsils. Thus, to address this gap in knowledge, we have studied the immune response to EBV infection using tonsil organoids as a model that allows us to address the greater systemic complexity present at the site of infection in the oropharynx. EBV infection is efficiently controlled when the tonsils are derived from "virus-experienced" individuals and CD8+ memory T lymphocytes expressing CD103 play a leading role in this immune response. In contrast, in primary infections, immune control of lymphoblastoid cell proliferation is much less effective, and a key factor restricting the immune response is the secretion of the immunomodulatory viral IL-10 molecule. These results highlight the importance of the host cytotoxic response at the site of infection and demonstrate that immune evasion molecules appear to be crucial for EBV-infected B cells to elude the local immune response and so disseminate the infection throughout the organism.

immunology↗

bioRxiv2025

A high-resolution, unbiased analysis of the cellular immune response to Epstein-Barr virus

More than 95% of humans are infected with Epstein-Barr virus (EBV), yet although EBV infection has been associated with inflammatory and autoimmune diseases, lymphoproliferative disorders, and several types of cancer, for the vast majority of infected people the infection is asymptomatic as EBV replication is controlled by the immune system. Immunity against this virus has been studied since the discovery of EBV in the 1960s, and although important insights have been made, no unbiased, global studies of immune responses to EBV in healthy seropositive subjects have been reported. Here we describe a novel protocol to study the cellular immune response to EBV, detecting lymphocytes that respond to EBV via analyses of proliferation or induced expression of activation markers and cytokines. Using this system we sequenced, for the first time at a single-cell level, the transcriptome of all cells capable of responding to EBV in healthy individuals and in patients with inborn errors of immunity (IEI) associated with susceptibility to EBV infection. Lymphocyte cytotoxicity appears to be crucial for the proper control of EBV-infection, while a proportionate T-regulatory cell response likely helps to avoid excessive immunity and immune pathology. We also show that {gamma}{delta} T cells expressing the TCR V{delta}1 chain use various activating natural killer (NK) cell receptors to recognise and kill EBV-infected lymphoblastoid cell lines (LCLs) and thus could be a promising candidate for allogeneic cell therapy for EBV-associated lymphoproliferative disorders in patients with either primary or secondary immunodeficiencies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/681317v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@116ad85org.highwire.dtl.DTLVardef@1da33d7org.highwire.dtl.DTLVardef@81a2a6org.highwire.dtl.DTLVardef@dd571d_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

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↗