Work

Marked variation in the susceptibility of HIV-1 to type 1 interferon inhibition during early, late and rebound infection

Year: 2019

Type: article

Abstract: Journal of Virus Eradication 2019; 5 (Supplement 3): 1-58 29 MDMs or human astrocytes.Both PacBio and MiSeq were respectively employed for sequencing full-length gp120 or V3 loop of HIV isolates.Results: Total 9 patients were selected for HIV outgrowth from the cells of lumbar-drained CSF and PBMCs; 7 of them had normal cognitive performance and two had HAND.Except for one case, HIV-1 RNA was not detected in blood and CSF.We isolated 7 HIV-1 strains, one from CSF cells and 6 from PBMCs in 5 patients including two with HAND.6 of 7 viruses were characterized for tropism, 5 were X4-tropic and one was R5-tropic.Interestingly, the patient with one isolate from CSF and 2 isolates from blood at two time-points had normal cognition and all of 3 viruses were X4-tropic.These 3 viruses and another one were further sequenced for full-length gp120 or V3 loop.Analysis of phylogenetic trees showed that CSF viral quasispecies were compartmentalized and could seed the periphery.Furthermore, three viruses from the single patient productively infected astrocytes via a transwell culture system where HIV-infected JKT cells were loaded on top chamber and only HIV particles could go through its membrane and reach astrocytes in bottom wells.This is consistent with prior observations that immature HIV particles released from HIV-infected lymphocytes were able to directly bind to CXCR4 on astrocytes leading to the infection in absence of CD4.Conclusions: X4-tropic viruses may predominate in the patients with long-term cART-suppressive therapy.X4 virus can be compartmentalized in the CSF and over a period of time seed the periphery.

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30148-5