Pulmonary Hypertension Associated With Human Immunodeficiency Virus: Uncovering Viral Evolution Via Bioinformatics

Individuals with Human Immunodeficiency Virus (HIV) are prone to illnesses like pulmonary hypertension (PH), despite the success of antiretrovirals. PH affects more HIV+ individuals (0.05%) than uninfected (0.001%). The causes of HIV‐PH are unknown however, studies suggest that HIV proteins may play a role. Recent studies found specific HIV‐ nef mutations associated with the PH phenotype in humans; others suggested that HIV Envelope (Env) induces PH‐like pulmonary vasculopathy in monkeys. We hypothesized that HIV‐PH‐specific mutations may also extend to env : HIV‐PH patients harbor Envelopes more fit to evade the immune system (more glycosylated), and more pathogenic (T‐tropic vs. M‐tropic), compared to controls. Preliminarily, we cloned HIV‐ env and nef from blood of eight HIV+ consenting subjects, and analyzed the env and nef sequences in silico, using tools available in the Los Alamos National Lab. We found more glycosylated Env and T‐tropic viruses along with mutations in Nef in HIV‐PH samples, suggesting that mutations in HIV, in the context of Pulmonary Hypertension, may also implicate Env; further studies may confirm dual evolution of HIV Env‐Nef in a larger sample size. These data may help to gain insights into the mechanisms involved in HIV‐Pulmonary Hypertension. This research was supported by UPR‐PRISE (NIH/NIGMS‐R25GM096955), NHLBI K01‐HL103196 (Almodóvar), and R01‐HL083491 (Flores).