2026-07-31T04:41:22Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1381022026-07-08T00:02:21Zcom_20.500.14352_14col_20.500.14352_15

HIV-1 envelope glycoprotein modulates CXCR4 clustering and dynamics on the T cell membrane. Quijada Freire, Adriana Santiago, César A. García Cuesta, Eva M. Soler Palacios, Blanca Ayala Bueno, Rosa Gardeta, Sofia R. San Sebastian, Enara Armendariz Burgoa, Eva Puertas, Maria Carmen Villares, Ricardo Garaigorta, Urtzi González Granado, Luis Ignacio Rodriguez Frade, Jose Miguel Chojnacki, Jakub Martínez Picado, Javier Mellado, Mario Artículo de acceso abierto publicado en eLife bajo licencia Creative Commons Attribution. La aportación demuestra que la glicoproteína Env del VIH-1 reorganiza la superficie de los linfocitos T CD4+ mediante agrupamiento específico de CD4 y CXCR4, generando una configuración favorable para la entrada viral. Luis Ignacio González-Granado participa como coautor clínico-inmunológico, aportando la interpretación traslacional de los hallazgos relacionados con CXCR4 y su conexión con el síndrome WHIM, enfermedad rara causada por mutaciones de este receptor. El trabajo conecta biología de membrana, virología e inmunodeficiencias primarias, y ha tenido impacto divulgativo mediante nota de prensa institucional de la Comunidad de Madrid. 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 human 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 CXCR4, 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. 2026-07-07T10:43:05Z 2026-07-07T10:43:05Z 2026-05-12 journal article Quijada-Freire A, Santiago CA, García-Cuesta EM, Soler Palacios B, Ayala-Bueno R, Gardeta SR, San Sebastian E, Armendariz-Burgoa E, Puertas MC, Villares R, Garaigorta U, González-Granado LI, Rodriguez Frade JM, Chojnacki J, Martinez-Picado J, Mellado M. HIV-1 envelope glycoprotein modulates CXCR4 clustering and dynamics on the T cell membrane. eLife. 2026;15:RP110354. doi: 10.7554/eLife.110354. PMCID: PMC13167113. 2050-084X 10.7554/eLife.110354.2 https://hdl.handle.net/20.500.14352/138102 https://doi.org/10.7554/eLife.110354.1 42118136 https://elifesciences.org/articles/110354 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International eLife Sciences Publications Ltd.