HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy.

Research highlights▶ Meninges harbor HIV-1 from both brain and peripheral tissues. ▶ Brain is capable of re-seeding the periphery with HIV-1. ▶ HIV-1 may enter the brain during various stages of HIV disease. ▶ Viruses with specific genetic signatures may be more neurotropic.