The paradox of HIV nef function: resolution of the contradictions

The function of nef, an accessory protein of HIV, has been highly controversial. Careful studies by respected investigators have ascribed diametrically opposed functions to nef with some groups claiming nef increases replication and viral infectivity while others argue nef inhibits replication and reduces infectivity. Replicative homeostasis resolves this superficially irreconcilable paradox, and indicates both positions could be true, if the exact function of nef is dependent on whether the nef tested is wild-type or variant with respect to the polymerase. The basis of resolution of the enigma posed by nef function is fundamental to and understanding of viral pathobiology.