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In vivo derived HIV-1 nef gene products are heterogeneous and lack detectable nucleotide binding activity.

Multiple HIV-1 nef genes were cloned from lymphocyte DNA of asymptomatic seropositive individuals by polymerase chain reaction (PCR). Sequence analysis of these clones revealed a unique set of nef variants with premature terminations (PCRnef 1 and 6), mutations at sites of potential posttranslational modification (PCRnef 2 and 3) and deletions. In common with laboratory isolates of nef, strong sequence conservation was observed in the central domain of nef and in the myristylation target sequence, with variable domains toward the N- and C-termini of the molecule. The biochemical function of nef remains elusive however, as the products of these genes cloned into a bacterial expression system failed to reveal any nucleotide binding activity.