Overexpression of the Interferon-Inducible Isoform 4 of NCOA7 Dissects the Entry Route of Enveloped Viruses and Demonstrates that HIV Enters Cells via Fusion at the Plasma Membrane.

The HIV-1 entry-route is a matter of ongoing controversy, and there is evidence for fusion either at the cell surface or from within endosomes. A recent report demonstrated that isoform 4 of nuclear receptor coactivator 7 (NCOA7iso4) interacts with endolysosomal vacuolar-type H⁺-ATPase (V-ATPase), increasing lytic activity and thereby severely affecting the entry of vesicular stomatitis virus glycoprotein (VSV-G)-mediated, but not HIV-Env-mediated, entry and infection. As basal expression of NCOA7iso4 is low in the absence of type-1 interferons, its overexpression is a novel tool to study viral entry.