Sequence variation occurs in CD4 epitopes during early HIV infection.
OBJECTIVE
To determine whether viral sequence variation occurs in HIV-specific CD4 epitopes during early HIV infection.


METHODS
Gag, Nef, and integrase (Int) sequences were obtained from the plasma of 7 subjects identified during acute HIV-1 infection. Changes in the viral sequence were determined based on comparison of sequences obtained at 2 time points during early infection. Peptide-specific CD4+ T-cell responses were measured at matched time points using interferon-gamma enzyme-linked immunosorbent spot assays to identify CD4 epitopes.


RESULTS
An average of 4 mutations were identified per subject. The majority of the mutations were nonsynonymous and resulted in a total of 6 amino acid changes in Gag, 7 changes in Nef, and 6 changes and a deletion in Int. Half of the sequence changes were within recognized CD4 epitopes. Mutations within CD4 epitopes were coincident with changes in the peptide-specific CD4 response.


CONCLUSIONS
These data indicate that sequence variation occurs within recognized CD4 epitopes during early HIV infection. Furthermore, it suggests that mutations within HIV-specific CD4 epitopes may affect T helper cell function.
Rychert
Jenna
J
Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Saindon
Suzanne
S
Placek
Sarah
S
Daskalakis
Demetre
D
Rosenberg
Eric
E
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015750:Genes, gag; D015754:Genes, nef; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D019426:Integrases / Q000235:genetics; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009154:Mutation
D015704:CD4 Antigens; D019426:Integrases