Expression of HIV envelope protein in the human central nervous system

The HIV envelope glycoprotein gp120 contributes to neuronal damage that could lead to HIV-mediated neurocognitive disorder. However, it is debated whether gp120 could promote direct neurotoxicity to synapses as it may not be present in the central nervous system of people with HIV (PWH) on antiretroviral therapy (ART). This study sought to establish whether gp120 is expressed in the human central nervous system in the pre-ART and post-ART era.

We utilized real-time PCR to detect the envelope mRNA in postmortem caudate nucleus from pre-ART era. HIV-negative samples were used as controls. We then used RNAscope fluorescence multiplex to identify which cells express the envelope mRNA. To determine whether gp120 is present despite ART, we analyzed cerebrospinal fluid (CSF) samples from PWH on ART using mass spectrometry.

Using PCR, we detected the envelope mRNA in the caudate nucleus from PWH with neurocognitive impairment but not in control samples. With RNAscope, we detected the envelope mRNA in microglia and astrocytes in the frontal cortex and caudate nucleus from HIV-positive tissue. With mass spectrometry, we identified a gp120 peptide in the CSF of PWH on antiretroviral therapy ( n  = 20) but not in control participants ( n  = 7).

Our data suggest that despite antiretroviral therapy, gp120 is expressed and likely released by infected cells, suggesting that gp120 could be one of the key factors in the neuropathology observed in PWH.