Distinct HIV-1 Population Structure across Meningeal and Peripheral T Cells and Macrophage Lineage Cells
Gonzalez-Perez, Maria Paz
Ganta, Krishna Kumar
Lamers, Susanna L
UMass Chan AffiliationsProgram in Molecular Medicine
Document TypeJournal Article
MetadataShow full item record
AbstractHIV-1 sequence population structure among brain and nonbrain cellular compartments is incompletely understood. Here, we compared proviral pol and env high-quality consensus single-molecule real-time (SMRT) sequences derived from CD3+ T cells and CD14+ macrophage lineage cells from meningeal or peripheral (spleen, blood) tissues obtained at autopsy from two individuals with viral suppression on antiretroviral therapy (ART). Phylogenetic analyses showed strong evidence of population structure between CD3+ and CD14+ virus populations. Distinct env variable-region characteristics were also found between CD3+ and CD14+ viruses. Furthermore, shared macrophage-tropic amino acid residues (env) and drug resistance mutations (pol) between meningeal and peripheral virus populations were consistent with the meninges playing a role in viral gene flow across the blood-brain barrier. Overall, our results point toward potential functional differences among meningeal and peripheral CD3+ and CD14+ virus populations and a complex evolutionary history driven by distinct selection pressures and/or viral gene flow. IMPORTANCE Different cell types and/or tissues may serve as a reservoir for HIV-1 during ART-induced viral suppression. We compared proviral pol and env sequences from CD3+ T cells and CD14+ macrophage lineage cells from brain and nonbrain tissues from two virally suppressed individuals. We found strong evidence of viral population structure among cells/tissues, which may result from distinct selective pressures across cell types and anatomic sites.
SourceRose R, Gonzalez-Perez MP, Nolan D, Ganta KK, LaFleur T, Cross S, Brody R, Lamers SL, Luzuriaga K. Distinct HIV-1 Population Structure across Meningeal and Peripheral T Cells and Macrophage Lineage Cells. Microbiol Spectr. 2022 Oct 26;10(5):e0250822. doi: 10.1128/spectrum.02508-22. Epub 2022 Sep 29. PMID: 36173332; PMCID: PMC9602438.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51782
RightsCopyright © 2022 Rose et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.; Attribution 4.0 International
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Except where otherwise noted, this item's license is described as Copyright © 2022 Rose et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.