Relative dominance of Env-gp41-specific cytotoxic T lymphocytes responses in HIV-1 advanced infection.
Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) responses provide an important defense in controlling HIV-1 replication, but they fail to control the progression of AIDS in advanced HIV-1 infection. To uncover the situation of these responses in patients with advanced HIV-1 infection, we assessed HIV-1-specific CTL responses in 20 individuals with advanced HIV-1 infection using 407 overlapping peptides spanning all expressed HIV-1 proteins using a gamma interferon-enzyme-linked immunospot (ELISpot) assay. In comparison to 20 individuals with moderately advanced HIV-1 infection, HIV-1-specific CTL responses were significantly decreased (P=0.044) and less peptides could be recognized (P=0.05) in advanced HIV-1 infection. Weakening of Env-gp120 and Gag-specific CTL responses contributed importantly to the decrease of CTL magnitude (P=0.042 and 0.078, respectively), while Env-gp41-specific CTL responses were relatively stronger during the end-stage of HIV-1 infection (P<0.001). Nef and Env-gp41 represented the most frequently targeted HIV-1 proteins in advanced HIV-1 infection. The entropy scores of peptides targeted in two groups were not significantly different. Only the breadth and magnitude of Env-gp41-specific CTL responses were positively correlated with viral loads in advanced HIV-1 infection (P=0.005 and 0.001, respectively). These findings suggest that progressive HIV-1 infection is associated with a weakening of Env-gp120- and Gag-specific CTL responses, and a simultaneous expansion of Env-gp41-specific CTL which is likely driven by high level viral replication.
Zhuang
Yan
Y
Department of Infectious Diseases, Tangdu Hospital Affiliated to the Fourth Military Medical University, PR China.
Sun
Yongtao
Y
Zhai
Song
S
Huang
Dedong
D
Zhao
Shuguang
S
Wang
Shaoyang
S
Kang
Wenzhen
W
Li
Xinhong
X
Walker
Bruce D
BD
Altfeld
Marcus
M
Yu
Xu G
XG
D000328:Adult; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load / Q000379:methods; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D054311:nef Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma