Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1
IntroductionHuman immunodeficiency virus type 1 (HIV-1) utilizes either the CCR5 (R5) or CXCR4 (X4) coreceptor for host cell entry. Coreceptor switching from R5 to X4 and elevated immune activation have been associated with disease progression. X4-tropic HIV-1 is predominantly observed in the late s...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1632287/full |
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| author | Francisco Xavier Guerra-Castillo Francisco Xavier Guerra-Castillo Sandra Pinto-Cardoso Santiago Ávila-Ríos Monserrat Chávez-Torres Amy Peralta-Prado Carolina González-Torres Javier Gaytán-Cervantes Brenda Requena-Benitez Dafne Díaz-Rivera Carmen Alaez-Verson María Concepción Hernández-García Vilma Carolina Bekker-Méndez |
| author_facet | Francisco Xavier Guerra-Castillo Francisco Xavier Guerra-Castillo Sandra Pinto-Cardoso Santiago Ávila-Ríos Monserrat Chávez-Torres Amy Peralta-Prado Carolina González-Torres Javier Gaytán-Cervantes Brenda Requena-Benitez Dafne Díaz-Rivera Carmen Alaez-Verson María Concepción Hernández-García Vilma Carolina Bekker-Méndez |
| author_sort | Francisco Xavier Guerra-Castillo |
| collection | DOAJ |
| description | IntroductionHuman immunodeficiency virus type 1 (HIV-1) utilizes either the CCR5 (R5) or CXCR4 (X4) coreceptor for host cell entry. Coreceptor switching from R5 to X4 and elevated immune activation have been associated with disease progression. X4-tropic HIV-1 is predominantly observed in the late stage of infection, when the immune environment characterized by chronic activation is optimal for their replication. The aim of this study was to determine viral tropism in late HIV presenters and who have not previously received treatment in Mexico City and its relationship with markers of chronic immune activation.MethodsA cross-sectional study was conducted on 122 people living with HIV (PLWH) recruited from two public health services. Viral tropism was determined using next-generation sequencing (NGS) and the geno2pheno algorithm. Immune activation was assessed through flow cytometry (CD38+, HLA-DR+), and soluble markers (sCD14, sCD163, IL-6) were quantified using enzyme-linked immunosorbent assays (ELISA). Differences in immune activation patterns between R5 and X4 group were explored using Mann-Whitney Wilcoxon test and t-test, and a principal component analysis (PCA). Logistic regression was used to evaluate associations between immune activation profiles and the presence of X4-tropic viruses.ResultsNinety-eight individuals had high-quality V3 loop sequences, 81.6% harbored only R5 variants (R5 group), while 18.4% had mixed R5/X4 populations (X4 group). Most PLWH had CD4+ T cell counts below 200 cells/µL, showing no significant difference between groups. Elevated levels of IL-6 were significantly associated with the R5 group (p = 0.01), while the X4 group showed increased expression of CD38+ and HLA-DR+CD38+ markers, although not statistically significant. Furthermore, IL-6 emerges as a negative predictor for the presence of X4 viruses (OR = 0.06, p = 0.006).ConclusionR5-tropic viruses are associated with elevated inflammatory responses in early stages, as indicated by higher IL-6 levels, while X4-tropic viruses may contribute to CD4+ T cell depletion through immune activation. Consequently, elevated levels of IL-6 emerge as a negative predictor for the presence of X4 viruses. The relationship between viral tropism and chronic immune activation in HIV-1 infection reflects a complex interplay which appears to be bidirectional. |
| format | Article |
| id | doaj-art-b48c743a449c4f3a803ffa2f459829ec |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b48c743a449c4f3a803ffa2f459829ec2025-08-20T03:17:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16322871632287Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1Francisco Xavier Guerra-Castillo0Francisco Xavier Guerra-Castillo1Sandra Pinto-Cardoso2Santiago Ávila-Ríos3Monserrat Chávez-Torres4Amy Peralta-Prado5Carolina González-Torres6Javier Gaytán-Cervantes7Brenda Requena-Benitez8Dafne Díaz-Rivera9Carmen Alaez-Verson10María Concepción Hernández-García11Vilma Carolina Bekker-Méndez12Unidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoLaboratorio de Secuenciación, División de Desarrollo de la Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, MexicoLaboratorio de Secuenciación, División de Desarrollo de la Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, MexicoUnidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoCentro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Ciudad de México, MexicoLaboratorio de Diagnóstico Genómico, Instituto Nacional de Médicina Genómica (INMEGEN), Ciudad de México, MexicoHospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoUnidad de Investigación Médica en Inmunología e Infectología, Hospital de Infectología “Dr. Daniel Méndez Hernández”, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, MexicoIntroductionHuman immunodeficiency virus type 1 (HIV-1) utilizes either the CCR5 (R5) or CXCR4 (X4) coreceptor for host cell entry. Coreceptor switching from R5 to X4 and elevated immune activation have been associated with disease progression. X4-tropic HIV-1 is predominantly observed in the late stage of infection, when the immune environment characterized by chronic activation is optimal for their replication. The aim of this study was to determine viral tropism in late HIV presenters and who have not previously received treatment in Mexico City and its relationship with markers of chronic immune activation.MethodsA cross-sectional study was conducted on 122 people living with HIV (PLWH) recruited from two public health services. Viral tropism was determined using next-generation sequencing (NGS) and the geno2pheno algorithm. Immune activation was assessed through flow cytometry (CD38+, HLA-DR+), and soluble markers (sCD14, sCD163, IL-6) were quantified using enzyme-linked immunosorbent assays (ELISA). Differences in immune activation patterns between R5 and X4 group were explored using Mann-Whitney Wilcoxon test and t-test, and a principal component analysis (PCA). Logistic regression was used to evaluate associations between immune activation profiles and the presence of X4-tropic viruses.ResultsNinety-eight individuals had high-quality V3 loop sequences, 81.6% harbored only R5 variants (R5 group), while 18.4% had mixed R5/X4 populations (X4 group). Most PLWH had CD4+ T cell counts below 200 cells/µL, showing no significant difference between groups. Elevated levels of IL-6 were significantly associated with the R5 group (p = 0.01), while the X4 group showed increased expression of CD38+ and HLA-DR+CD38+ markers, although not statistically significant. Furthermore, IL-6 emerges as a negative predictor for the presence of X4 viruses (OR = 0.06, p = 0.006).ConclusionR5-tropic viruses are associated with elevated inflammatory responses in early stages, as indicated by higher IL-6 levels, while X4-tropic viruses may contribute to CD4+ T cell depletion through immune activation. Consequently, elevated levels of IL-6 emerge as a negative predictor for the presence of X4 viruses. The relationship between viral tropism and chronic immune activation in HIV-1 infection reflects a complex interplay which appears to be bidirectional.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1632287/fullHIV-1 tropismCXCR4CCR5chronic immune activationIL-6CD38 |
| spellingShingle | Francisco Xavier Guerra-Castillo Francisco Xavier Guerra-Castillo Sandra Pinto-Cardoso Santiago Ávila-Ríos Monserrat Chávez-Torres Amy Peralta-Prado Carolina González-Torres Javier Gaytán-Cervantes Brenda Requena-Benitez Dafne Díaz-Rivera Carmen Alaez-Verson María Concepción Hernández-García Vilma Carolina Bekker-Méndez Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 Frontiers in Immunology HIV-1 tropism CXCR4 CCR5 chronic immune activation IL-6 CD38 |
| title | Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 |
| title_full | Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 |
| title_fullStr | Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 |
| title_full_unstemmed | Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 |
| title_short | Patterns of inflammation and immune activation by coreceptor use in people living with HIV-1 |
| title_sort | patterns of inflammation and immune activation by coreceptor use in people living with hiv 1 |
| topic | HIV-1 tropism CXCR4 CCR5 chronic immune activation IL-6 CD38 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1632287/full |
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