HIV X4 Viruses as Potential Agents in the Pathophysiology of HIV-associated Pulmonary Hypertension

Pulmonary Hypertension (PH) is a severe disease that is more frequent in HIV+ individuals even with antiretrovirals. We do not know how HIV contributes to HIV-PH. HIV proteins like gp120 play roles in the pathogenesis of HIV-PH. Recently, we found that CXCR4-utilizing HIV variants (X4) are overrepresented in patients with HIV-PH compared to CCR5-using HIV(R5). Hence, our objective was to determine if there is a differential impact of HIV-X4 or R5 on pulmonary endothelial cells (EC). For this, we exposed cultured human pulmonary EC to recombinant HIV gp120 X4 or R5, and PBS (mock). We measured the activity of caspases 3/7 (a marker of apoptosis) from 4-48 hrs. We also examined gene expression in EC exposed to gp120, by PCR array. We found increased caspase 3/7 activity in all EC at 8 hrs (initial apoptotic wave); this activity decreased to baseline at 16 hrs and increased again at 24 hrs (second apoptotic wave). Compared to X4, R5 gp120 induced slightly more apoptosis in EC at 8 hrs (p=0.20) and 48 hrs (p=...