HIV-1-specific CD4+ T-cell responses are not associated with significant viral epitope variation in persons with persistent plasma viremia.
OBJECTIVE
To determine whether increased sequence variation occurs in regions of endogenous HIV-1 targeted by HIV-1-specific CD4 T cells. The presence of increased variation would be suggestive of immune evasion by HIV-1.


METHODS
We performed a cross-sectional study of untreated HIV-1-infected subjects measuring HIV-1-specific interferon (IFN)-gamma-secreting CD4 T-cell responses against epitopes in Gag p17 and p24 and concurrent endogenous plasma HIV-1 RNA epitope sequence variation.


METHODS
CD8- depleted IFNgamma enzyme-linked immunospot assays were used to identify regions of HIV-1 Gag recognized by CD4 T cells. Reverse transcriptase polymerase chain reaction and TA cloning were used to sequence endogenous plasma HIV-1 virus and identify variants.


RESULTS
CD4 T-cell epitopes in Gag p17 and p24 were identified in 5 individuals, and concurrent sequence information on endogenous HIV-1 was obtained in 4 of these individuals. Endogenous plasma HIV-1 RNA sequencing revealed no intrapatient amino acid sequence variation through identified epitopes.


CONCLUSIONS
In these chronically infected viremic subjects, circulating IFNgamma-secreting CD4 T-cell responses were directed against epitope sequences found in the predominant strain of endogenous circulating plasma HIV-1, suggesting that escape from CD4 T-cell responses is not a common process in vivo.
Koeppe
John R
JR
Division of Infectious Diseases and Clinical Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. John.Koeppe@uchsc.edu
Campbell
Thomas B
TB
Rapaport
Eric L
EL
Wilson
Cara C
CC
D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D018984:Epitopes, T-Lymphocyte / Q000235:genetics*; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D014644:Genetic Variation; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014764:Viral Proteins / Q000276:immunology*; D014766:Viremia / Q000276:immunology* / Q000821:virology*; D054301:gag Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D007371:Interferon-gamma