Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection.
Cytotoxic T lymphocytes (CTLs) are thought to play a crucial role in the termination of the acute primary HIV-1 syndrome, but clear evidence for this presumption has been lacking. Here we demonstrate positive selection of HIV-1 proviral sequences encoding variants within a CTL epitope in Nef, a gene product critical for viral pathogenicity, during and after seroconversion. These positively selected HIV-1 variants carried epitope sequence changes that either diminished or escaped CTL recognition. Other proviruses had mutations that abolished the Nef epitope altogether. These results provide clear evidence that CTLs exert selection pressure on the viral population in acute HIV-1 infection.
Price
D A
DA
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
Goulder
P J
PJ
Klenerman
P
P
Sewell
A K
AK
Easterbrook
P J
PJ
Troop
M
M
Bangham
C R
CR
Phillips
R E
RE
D000328:Adult; D000595:Amino Acid Sequence; D002999:Clone Cells; D003001:Cloning, Molecular; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005838:Genotype; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D012641:Selection, Genetic; D017421:Sequence Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015693:Gene Products, nef; D015488:HIV Antigens; D006680:HLA Antigens; D010455:Peptides; D054311:nef Gene Products, Human Immunodeficiency Virus