Distinct HIV-1 population structure across meningeal and peripheral T cells and macrophage-lineage cells

We compared proviral pol and env high quality consensus Single Molecular 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 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 towards 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.