Guerra-Castillo Francisco Xavier, Pinto-Cardoso Sandra, Ávila-Ríos Santiago, Chávez-Torres Monserrat, Peralta-Prado Amy, González-Torres Carolina, Gaytán-Cervantes Javier, Requena-Benitez Brenda, Díaz-Rivera Dafne, Alaez-Verson Carmen, Hernández-García María Concepción, Bekker-Méndez Vilma Carolina
Unidad 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, Mexico.
Posgrado en Ciencias Biológicas, Unidad de Posgrado, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.
Front Immunol. 2025 Jul 10;16:1632287. doi: 10.3389/fimmu.2025.1632287. eCollection 2025.
Human 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.
A 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.
Ninety-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).
R5-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.
1型人类免疫缺陷病毒（HIV-1）利用CCR5（R5）或CXCR4（X4）共受体进入宿主细胞。共受体从R5向X4的转换以及免疫激活增强与疾病进展相关。X4嗜性HIV-1主要在感染后期出现，此时以慢性激活为特征的免疫环境最适合其复制。本研究的目的是确定墨西哥城未接受过治疗的晚期HIV感染者的病毒嗜性及其与慢性免疫激活标志物的关系。
对从两个公共卫生服务机构招募的122名HIV感染者（PLWH）进行了一项横断面研究。使用下一代测序（NGS）和geno2pheno算法确定病毒嗜性。通过流式细胞术（CD38+、HLA-DR+）评估免疫激活，并使用酶联免疫吸附测定（ELISA）对可溶性标志物（sCD14、sCD163、IL-6）进行定量。使用Mann-Whitney Wilcoxon检验和t检验以及主成分分析（PCA）探讨R5和X4组之间免疫激活模式的差异。使用逻辑回归评估免疫激活谱与X4嗜性病毒存在之间的关联。
98名个体具有高质量的V3环序列，81.6%仅携带R5变体（R5组），而18.4%具有R5/X4混合群体（X4组）。大多数PLWH的CD4+T细胞计数低于200个细胞/µL，两组之间无显著差异。IL-6水平升高与R5组显著相关（p = 0.01），而X4组的CD38+和HLA-DR+CD38+标志物表达增加，尽管无统计学意义。此外，IL-6是X4病毒存在的负预测因子（OR = 0.06，p = 0.006）。
如较高的IL-6水平所示，R5嗜性病毒与早期炎症反应增强相关，而X4嗜性病毒可能通过免疫激活导致CD4+T细胞耗竭。因此，IL-6水平升高是X4病毒存在的负预测因子。HIV-1感染中病毒嗜性与慢性免疫激活之间的关系反映了一种似乎是双向的复杂相互作用。
