Complexo Hospital de Clínicas-UFPR, Seção de Virologia, Setor Análises Clínicas, Rua Padre Camargo, 280, Curitiba, PR, 80060-240, Brazil.
Immunophenotyping Laboratory, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
J Neurovirol. 2023 Jun;29(3):308-324. doi: 10.1007/s13365-023-01137-z. Epub 2023 May 23.
CD14CD16 monocytes are susceptible to HIV-1 infection, and cross the blood-brain barrier. HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared to HIV-1B, which might influence monocyte trafficking into the CNS. We hypothesized that the proportion of monocytes in CSF in HIV-1C is lower than HIV-1B group. We sought to assess differences in monocyte proportions in cerebrospinal fluid (CSF) and peripheral blood (PB) between people with HIV (PWH) and without HIV (PWoH), and by HIV-1B and -C subtypes. Immunophenotyping was performed by flow cytometry, monocytes were analyzed within CD45 + and CD64 + gated regions and classified in classical (CD14CD16), intermediate (CD14CD16), and non-classical (CD14CD16). Among PWH, the median [IQR] CD4 nadir was 219 [32-531] cell/mm; plasma HIV RNA (log) was 1.60 [1.60-3.21], and 68% were on antiretroviral therapy (ART). Participants with HIV-1C and -B were comparable in terms of age, duration of infection, CD4 nadir, plasma HIV RNA, and ART. The proportion of CSF CD14CD16 monocytes was higher in participants with HIV-1C than those with HIV-1B [2.00(0.00-2.80) vs. 0.00(0.00-0.60) respectively, p = 0.03 after BH correction p = 0.10]. Despite viral suppression, the proportion of total monocytes in PB increased in PWH, due to the increase in CD14CD16 and CD14CD16 monocytes. The HIV-1C Tat substitution (C30S31) did not interfere with the migration of CD14CD16 monocytes to the CNS. This is the first study to evaluate these monocytes in the CSF and PB and compare their proportions according to HIV subtype.
CD14CD16 单核细胞容易感染 HIV-1,并且可以穿过血脑屏障。与 HIV-1B 相比,HIV-1 亚型 C(HIV-1C)的 Tat 蛋白趋化活性降低,这可能会影响单核细胞向中枢神经系统的迁移。我们假设 HIV-1C 患者的 CSF 中单核细胞的比例低于 HIV-1B 组。我们试图评估 HIV-1B 和 HIV-1C 亚型的 HIV 感染者(PWH)和非 HIV 感染者(PWoH)的 CSF 和 PB 中单核细胞比例的差异。通过流式细胞术进行免疫表型分析,在 CD45+和 CD64+门内分析单核细胞,并分为经典(CD14CD16)、中间(CD14CD16)和非经典(CD14CD16)。在 PWH 中,中位数[IQR]CD4 最低点为 219[32-531]个细胞/mm;血浆 HIV RNA(log)为 1.60[1.60-3.21],68%的人正在接受抗逆转录病毒治疗(ART)。在年龄、感染持续时间、CD4 最低点、血浆 HIV RNA 和 ART 方面,HIV-1C 和 HIV-1B 的参与者具有可比性。HIV-1C 组参与者的 CSF CD14CD16 单核细胞比例高于 HIV-1B 组[分别为 2.00(0.00-2.80)和 0.00(0.00-0.60),BH 校正后 p 值为 0.03,p 值为 0.10]。尽管病毒得到抑制,但由于 CD14CD16 和 CD14CD16 单核细胞的增加,PWH 的 PB 中总单核细胞的比例增加。HIV-1C Tat 替代(C30S31)并未干扰 CD14CD16 单核细胞向中枢神经系统的迁移。这是第一项评估 CSF 和 PB 中这些单核细胞并根据 HIV 亚型比较其比例的研究。