ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF GENE-SEQUENCES PRESENT IN-VIVO

The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV- 1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) en code a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corresponding protein sequences of n aturally occurring nef genes obtained from several HIV-1-infected indi viduals. A consensus Nef sequence was derived and used to identify sev eral features that were highly conserved among the Nef sequences. Thes e features included a nearly invariant myristylation signal, regions o f sequence polymorphism and variable duplication, a region with an aci dic charge, a (Pxx)4 repeat sequence, and a potential protein kinase C phosphorylation site. Clustering of premature stop codons at position 124 was noted in 6 of the 54 Nef sequences. Further analysis revealed four stretches of residues that were highly conserved not only among the patient-derived HIV-1 Nef sequences, but also among the Nef sequen ces of HIV-2 and the SIVs, suggesting that Nef proteins expressed by t hese retroviruses are functionally equivalent. The ''Nef-defining'' se quences were used to evaluate the sequence alignments of known protein s reported to share sequence similarity with Nef sequences and to cond uct additional computer-based searches for similar protein sequences. A gene encoding the consensus Nef sequence was also generated. This ge ne encodes a full-length Nef protein that should be a valuable tool in further studies of Nef function.