title: Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression.
abstract: BACKGROUND
  The nef gene from HIV-1 has been shown to be an important pathogenic factor when considering development of AIDS. Detection of nef variants with an effect on immune modulation is important to understand HIV-1 pathogenesis and has possible impact on treatment strategies.
  
  
  METHODS
  The nef gene of HIV-1 isolates from patients in a long-term non-progressor (LTNP) cohort and a slow-progressor (SP) cohort (n = 11) was analysed and compared with isolates from a control patient group of progressors (n = 18). Most of the patients with delayed disease progression had extensive medical records, providing an insight into the LTNP disease profile and allowing for the stratification of patients based on their CD4 cell decline.
  
  
  RESULTS
  In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in HIV-1 Nef. The allelic frequency of cysteine 138 between the delayed disease progression group and the progressor group was found to be statistically significant (P = 0.0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently.
  
  
  CONCLUSIONS
  The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased viral replication (Premkumar DR, et al. AIDS Res Hum Retroviruses 1996; 12(4): 337-45). A sequence database search for comparative mutations revealed a high frequency of cysteine 138 in patients with reported SP AIDS.
authors.affiliation: Department of Infectious Diseases, Skejby Hospital, 8200 Aarhus, Denmark. mt@m.au.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Tolstrup
authors.forename: Alex L
authors.initials: AL
authors.lastname: Laursen
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Finn S
authors.initials: FS
authors.lastname: Pedersen
authors.forename: Lars
authors.initials: L
authors.lastname: Ostergaard
authors.forename: Mogens
authors.initials: M
authors.lastname: Duch
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003545:Cysteine / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D015754:Genes, nef / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic
chemical_list: D003545:Cysteine