Evolution of the HIV-1 nef gene in HLA-B*57 positive elite suppressors.
Elite controllers or suppressors (ES) are HIV-1 infected patients who maintain viral loads of < 50 copies/ml without antiretroviral therapy. CD8+ T cells are thought to play a key role in the control of viral replication and exert selective pressure on gag and nef in HLA-B*57 positive ES. We previously showed evolution in the gag gene of ES which surprisingly was mostly due to synonymous mutations rather than non-synonymous mutation in targeted CTL epitopes. This finding could be the result of structural constraints on Gag, and we therefore examined the less conserved nef gene. We found slow evolution of nef in plasma virus in some ES. This evolution is mostly due to synonymous mutations and occurs at a rate similar to that seen in the gag gene in the same patients. The results provide further evidence of ongoing viral replication in ES and suggest that the nef and gag genes in these patients respond similarly to selective pressure from the host.
Department of Medicine, Johns Hopkins University School of Medicine, 733 N, Broadway, Baltimore, MD 21205, USA.
Maria
M
Salgado
Timothy P
TP
Brennan
Karen A
KA
O'Connell
Justin R
JR
Bailey
Stuart C
SC
Ray
Robert F
RF
Siliciano
Joel N
JN
Blankson
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D000939:Epitopes / Q000235:genetics; D019143:Evolution, Molecular; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014779:Virus Replication / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
D000939:Epitopes; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D054311:nef Gene Products, Human Immunodeficiency Virus