Nup62 is essential for vRNA nuclear export and virus infectivity. Mock- and HIV-1–transfected HeLa cells were depleted of Nup62 and Nup107 using siRNA. (A) Western analysis for Nup62, Nup107, pr55Gag, and Nucleolin (loading control). (B) Effects of Nup62 and Nup107 KDs on virus production, TZM-bl FLuc activity, and infectivity. Protease(−) and Envelope(−) virus were used as negative infectivity controls. Error bars represent SD. (C) IF/FISH analysis of Nup62, Nup107, vRNA, DAPI, and DIC. Percentages in the vRNA column represent the frequency observed for each condition, and n = 500 vRNA-positive cells in three independent experiments. Bars, 10 µm. (D) A predictive model on how viruses may exploit encapsidated Nup62. Integrated proviral DNA (green; 1) is transcribed into vRNA (squiggly green) that is then exported with Nup62 (purple) to the cytoplasm as an RNP (2). vRNA dimerizes and is encapsidated into budding virus (3) that can now infect new cells, in which Nup62 may promote efficient nuclear import of the PIC (4) and integration into the host DNA (5). Cyt, cytoplasm; NE, nuclear envelope; Nuc, nucleus; PM, plasma membrane.