4.1 Article

Cerebrospinal fluid CD14++CD16+ monocytes in HIV-1 subtype C compared with subtype B

Journal

JOURNAL OF NEUROVIROLOGY
Volume 29, Issue 3, Pages 308-324

Publisher

SPRINGER
DOI: 10.1007/s13365-023-01137-z

Keywords

Cerebrospinal fluids (CSF); HIV subtypes; Flow cytometry; Monocytes; Intermediate; Non-classical

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This study investigated the proportion differences of monocytes in cerebrospinal fluid (CSF) and peripheral blood (PB) between individuals with HIV-1C and HIV-1B subtypes, and found a higher proportion of CD14(++)CD16(+) monocytes in the CSF of HIV-1C patients. Furthermore, despite viral suppression, the total monocyte proportion in PB increased in people with HIV due to the increase in CD14(++)CD16(+) and CD14(low)CD16(+) monocytes.
CD14(++)CD16(+) 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 (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), and non-classical (CD14(low)CD16(+)). Among PWH, the median [IQR] CD4 nadir was 219 [32-531] cell/mm(3); plasma HIV RNA (log(10)) 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 CD14(++)CD16(+) 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 CD14(++)CD16(+) and CD14(low)CD16(+) monocytes. The HIV-1C Tat substitution (C30S31) did not interfere with the migration of CD14(++)CD16(+) 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.

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