biostudies-literatureArmani-Tourret MINSERMInstituto de Salud Carlos IIIAgence Nationale de la RechercheAgence Nationale de Recherches sur le Sida et les Hépatites ViralesUniversité Toulouse III - Paul SabatierInstitut PasteurSidactione1009526https://www.ebi.ac.uk/biostudies/studies/S-EPMC8084328biostudies-literatureUnknown17(4)HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over tiPLoS pathogensMechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis.PMC8084328AAP-2013-2 and ECTZ63419RD16CIII/0002/0001ANR-10-LABX-69-01PI19CIIII/0004Staropoli IPerez-Olmeda MAssoumou LLevy YBenureau YArmani-Tourret MGasser RAlcami JMouquet HGarcia-Perez JLagane BZhou ZLorin VPuissant-Lubrano BArenzana-Seisdedos FCantaloube-Ferrieu VMartin-Blondel GIzopet JColin PDelaugerre CLelievre JDfalseMechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis.HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over ti2021-01-01T00:00:00Z2021 Apr2026-05-08T10:55:30.153Z2025-02-19T00:19:01.271ZS-EPMC80843283387232910.1371/journal.ppat.1009526