Relative Dominance of Env-gp41-Specific Cytotoxic T Lymphocytes Responses in HIV-1 Advanced Infection

Author(s): Yan Zhuang, Yongtao Sun, Song Zhai, Dedong Huang, Shuguang Zhao, Shaoyang Wang, Wenzhen Kang, Xinhong Li, Bruce D. Walker, Marcus Altfeld, Xu G. Yu.

Journal Name: Current HIV Research

Volume 6 , Issue 3 , 2008

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Abstract:

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 Envgp41- 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.

Keywords: Advanced HIV-1 infection, cytotoxic T-lymphocyte, cellular immune responses, HIV-1 Env-gp41

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Article Details

VOLUME: 6
ISSUE: 3
Year: 2008
Page: [239 - 245]
Pages: 7
DOI: 10.2174/157016208784324921
Price: $58