A VSV-G pseudotyped HIV vector mediates efficient transduction of human pulmonary artery smooth muscle cells

Attempts were made to infect human vascular smooth muscle cells derived fro m the pulmonary artery (hPASMC) with two different human immunodeficiency v irus (HIV) vector systems. ADA/Luc or HXB2/Luc were generated by cotransfec tion of luciferase reporter gene vector, pNL4-3-Luc-E-R-, and one of two en velope expressing vectors, pSMADA (R5) or pSMHXB2 (X4), The VSV-G/Luc or VS V-G/GFP were produced by a three-plasmid expression system which consisted of vesicular stomatitis virus G protein (VSV-G) expressing vector, packagin g plasmid, and one of two reporter genes (pHR'-CMV-Luc or pHR'-CMV-GFP), We used hPASMC, U87.CD4.CCR5 and U87.CD4.CXCR4 for infection. Neither ADA/Luc nor HXB2/Luc could infect hPASMC, though they could infect U87.CD4 with co rresponding coreceptors, On the other hand, the transduction of both VSV-G/ Luc and VSV-G/GFP to hPASMC was remarkable, At day 3, the relative proporti on of positive cells of hPASMC infected with VSV-G/GFP was 15%, The above f inding indicates a direct role of HIV-1 infection in pulmonary hypertension 'a rare complication of HIV-1 infection' and HIV-based vectors could intro duce foreign genes into hPASMC for gene therapy of pulmonary hypertension.