Restoration of wild-type infectivity to human immunodeficiency virus type 1 strains lacking nef by intravirion reverse transcription

Human immunodeficiency virus type 1 (HIV-1) Nef protein exerts several effe cts, both on infected cells and as a virion protein, which work together to enhance viral replication. One of these activities is the ability to enhan ce infectivity and the formation of proviral DNA. The mechanism of this enh ancement remains incompletely understood. We show that virions with nef del eted can be restored to wild-type infectivity by stimulating intravirion re verse transcription. Particle composition and measures of reverse transcrip tase activity remain the same for Nef(+) and Nef(-) virions both before and after natural endogenous reverse transcription (NERT) treatment. The effec t of NERT treatment on virions pseudotyped with murine leukemia virus envel ope protein was similar to that on particles pseudotyped with HIV-1 envelop e protein. However, virions pseudotyped with vesicular stomatitis virus G e nvelope protein showed no influence of Nef on NERT enhancement of infectivi ty. These observations suggest that Nef may function at a level prior to re verse transcription. Since NERT treatment results in partial disassembly of the viral core, we speculate that Nef may function at the level of core pa rticle disassembly.