Analysis of the HIV-1 nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy

Great variability in the course of human immunodeficiency virus type 1 (HIV -1) infection results from a complex interplay between host and virus facto rs. Some of the patients with prolonged nonprogressive infection have been reported to harbor virus variants with gross deletions in the accessory nef gene that has been implicated in in vivo pathogenicity in simian and mouse models. To investigate the role of nef-deleted HIV-1 in long-term nonprogr essor (LTNP) drug addicts in Italy the nef sequence from proviral DNA was a nalyzed from five LTNPs and five rapid progressor controls. Only small (2-1 2 amino acids) in-frame deletions and insertions were detected in the N-ter minal polymorphic and variable regions obtained from three LTNPs and one ra pid progressor. There was no evidence of premature termination of the Nef p rotein and all of the identified functional motifs were well conserved in b oth groups. Phylogenetic analysis showed interdigitation of nef sequences o btained from LTNPs and rapid progressors. The nef sequence of one LTNP, how ever, diverged significantly from those of the other patients. Availability of two additional blood DNA samples obtained previously from this subject allowed to detect evolution of nef at 14-17 years of HIV-1 infection, inclu ding progressive deletions. Although alterations of nef may be relatively f requent and continue to evolve in LTNPs, this study of a small number of pa tients does not indicate that gross deletions or loss of functional motifs play a major role in delaying or halting disease progression in infected dr ug abusers in Italy. J. Med. Virol. 60:294-299, 2000. (C) 2000 Wiley-Liss, Inc.