Sequence variations in human immunodeficiency virus type 1 Nef are associated with different stages of disease.
nef alleles derived from a large number of individuals infected with human immunodeficiency virus type 1 (HIV-1) were analyzed to investigate the frequency of disrupted nef genes and to elucidate whether specific amino acid substitutions in Nef are associated with different stages of disease. We confirm that deletions or gross abnormalities in nef are rarely present. However, a comparison of Nef consensus sequences derived from 41 long-term nonprogressors and from 50 individuals with progressive HIV-1 infection revealed that specific variations are associated with different stages of infection. Five amino acid variations in Nef (T15, N51, H102, L170, and E182) were more frequently observed among nonprogressors, while nine features (an additional N-terminal PxxP motif, A15, R39, T51, T157, C163, N169, Q170, and M182) were more frequently found in progressors. Strong correlations between the frequency of these variations in Nef and both the CD4(+)-cell count and the viral load were observed. Moreover, analysis of sequential samples obtained from two progressors revealed that several variations in Nef, which were more commonly observed in patients with low CD4(+)-T-cell counts, were detected only during or after progression to immunodeficiency. Our results indicate that sequence variations in Nef are associated with different stages of HIV-1 infection and suggest a link between nef gene function and the immune status of the infected individual.
Kirchhoff
F
F
Institute for Clinical and Molecular Virology, Friedrich-Alexander University, D-91054 Erlangen, Germany. fkkirchh@viro.med.uni-erlangen.de
Easterbrook
P J
PJ
Douglas
N
N
Troop
M
M
Greenough
T C
TC
Weber
J
J
Carl
S
S
Sullivan
J L
JL
Daniels
R S
RS
D000163:Acquired Immunodeficiency Syndrome / Q000821:virology; D000595:Amino Acid Sequence; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004279:DNA, Viral; D018450:Disease Progression; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics*; D005814:Genes, Viral; D014644:Genetic Variation; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D019562:Viral Load; D054311:nef Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus