Journal
AIDS RESEARCH AND HUMAN RETROVIRUSES
Volume 39, Issue 4, Pages 166-175Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/aid.2022.0022
Keywords
HAND; Vpr; entropy; signature amino acid residue; tyrosine; histidine
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There is increasing evidence that HIV-1 viral protein R (Vpr) is involved in the development of cognitive impairment. This study investigated the relationship between sequence variation in HIV-1 subtype C Vpr and HIV-associated neurocognitive impairment. The results showed that a tyrosine at position 45 (45Y) was a marker for neurocognitive impairment, while a histidine (45H) was a marker for non-impaired individuals. Furthermore, specific Vpr fragment sequences were associated with higher viral load and proviral load.
There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 subtype C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment-naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a tyrosine at position 45 (45Y) as a signature for neurocognitive impairment and histidine (45H) as a signature in the non-impaired individuals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load, and 60% lower absolute CD4-T cell count compared with those without the signature. Additionally, we identified four conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5-21), LGQYIY (42-47), TYGDTW (49-54), and PEDQGPQREPYNEW (5-18), that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitive impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery.
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