Specific amino acids in HIV-1 Vpr are significantly associated with changes in patient neurocognitive status. Human immunodeficiency virus 1 strain:Subtype B

Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50% of well-controlled HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND, bioinfomatic analyses were used to correlate peripheral blood-derived vpr sequences from well-controlled HIV-1-infected patients with changes in their neurocognitive abilities, as measured by comprehensive neurological testing and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between changes in GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences (niVpr variants). Amino acids 41-N, and 55-A in the primary Vpr sequence were associated with increased neurocognitive deficits and higher GDS. In contrast, amino acids 37-I and 41-S were connected to measureable reductions in GDS. niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain.