| Autor: |
Gumbs, Stephanie B. H., Stam, Arjen J., Mudrikova, Tania, Schipper, Pauline J., Hoepelman, Andy I. M., van Ham, Petra M., Borst, Anne L., Hofstra, LMarije, Gharu, Lavina, van Wyk, Stephanie, Wilkinson, Eduan, de Witte, Lot D., Wensing, Annemarie M. J., Nijhuis, Monique |
| Předmět: |
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| Zdroj: |
Journal of NeuroVirology; Aug2024, Vol. 30 Issue 4, p380-392, 13p |
| Abstrakt: |
Despite antiretroviral therapy (ART), HIV persistence in the central nervous system (CNS) continues to cause a range of cognitive impairments in people living with HIV (PLWH). Upon disease progression, transmigrating CCR5-using T-cell tropic viruses are hypothesized to evolve into macrophage-tropic viruses in the CNS that can efficiently infect low CD4-expressing cells, such as microglia. We examined HIV-1 RNA concentration, co-receptor usage, and CSF compartmentalization in paired CSF and blood samples from 19 adults not on treatment. Full-length envelope CSF- and plasma-derived reporter viruses were generated from 3 subjects and phenotypically characterized in human primary CD4+ T-cells and primary microglia. Median HIV RNA levels were higher in plasma than in CSF (5.01 vs. 4.12 log10 cp/mL; p = 0.004), and coreceptor usage was mostly concordant for CCR5 across the paired samples (n = 17). Genetically compartmentalized CSF viral populations were detected in 2 subjects, one with and one without neurological symptoms. All viral clones could replicate in T-cells (R5 T cell-tropic). In addition, 3 CSF and 1 plasma patient-derived viral clones also had the capacity to replicate in microglia/macrophages and, therefore have an intermediate macrophage tropic phenotype. Overall, with this study, we demonstrate that in a subset of PLWH, plasma-derived viruses undergo genetic and phenotypic evolution within the CNS, indicating viral infection and replication in CNS cells. It remains to be studied whether the intermediate macrophage-tropic phenotype observed in primary microglia represents a midpoint in the evolution towards a macrophage-tropic phenotype that can efficiently replicate in microglial cells and propagate viral infection in the CNS. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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