| As a major public health problem worldwide, acquired immunodeficiency syndrome (AIDS) has deprived more than 40 million lives. Highly active antiretroviral therapy (HAART) inhibits the replication of HIV-1, partly rebuilds the function of the immune system, cuts down the mobility of diseases associated with HIV, but the high cost, severe side effects, increasing emergence of drug-resistant viral strains and bad adherence limit the effect of HAART. A safe and effective vaccine to control HIV-1 and prevent it from spreading is the best way to conquer HIV/AIDS.Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of HIV-1 and SIV infection. The strategy to elicit potent CTL responses against HIV has become the current focus in HIV-1 vaccine research. The protein Nef is one of the proteins expressed during early infection and the first targeted protein recognized by CTL after HIV-1 infection. Now, it has been demonstrated that Nef can activate CD4+T lymphocytes, increase the transmissibility of viral particles and internalize the CD4 receptors and MHC, and prevent cell apoptosis. The Vpu protein also down regulates the CD4 molecule on the cell surface by interfering with the transport of the newly synthesized CD4 or by internalization of the CD4. Vpr inhibits the proliferation of the primary CD4+ lymphocytes, T-cell lines and other cells by inducing G2 cell cycle arrest, which appears to be mediated via a direct interaction between Vpr and the cyclin-dependent kinase subunit p34CDC2. Vpr functions in the nuclear localization and import of the HIV-1 preintegrated complex, which allows HIV-1 to infect and replicate in noproliferated cells. Vif promotes viral replication in vivo and serves a critical function for the productive infection of non-permissive cells, like peripheral blood mononuclear cells (PBMC). Vif functions to counteract an anti-retroviral cellular factor named APOBEC3G in non-permissive cells. The current mechanism proposed for protection of the virus by HIV-1 Vif is to induce APOBEC3G degradation through a ubiquitination-dependent proteasomal pathway.In this study, 61 HIV-1 infected individuals or AIDS patients and 10 HIV negative healthy volunteers were enrolled and CD4 cell counts and viral loads were detected. PBMC were separated from the subjects by Ficoll-Hypaque density gradient centrifugation and 142 overlapping peptides synthesized according to the HIV-1 clade B (HIV-1B) and HIV-1 clade C(HIV-1C) consensus sequence spanning the entire accessory protein region, were used to induce the HIV-1 accessory specific CD8+T cells secreting interferon gamma (IFN-γ) and detected by enzyme-linked immunospot (ELISpot) assay.The results show that either HIV-1B or HIV-1C accessory proteins serve as targets for HIV-1-specific CTL, especially the peptides within the Nef region which targeted at a higher cumulative magnitude and wider frequency than the other accessory proteins(P<0.001). The cumulative magnitude and frequency of CTL responses between clade B and C are not significantly different(P>0.05), including the immunodominant domains. The cumulative magnitude of HIV-1–specific CD8+T-cell responses to accessory proteins of HIV-1B or HIV-1C contribute nearly 21% of the total HIV-1–specific CTL response. These data indicate that, despite the small sizes of these accessory proteins targeted by CTL in natural HIV-1 infection, these proteins contribute considerably to the total HIV-1–specific CD8+ T-cell responses.Overall, this study has indentified the characteristics of specific CTL responses to HIV-1 accessory proteins and several immunodominant regions within the accessory proteins have been identified for further screening for CTL epitopes. HIV-1 accessory proteins prove to be a component in the induction of CTL responses. This study provided theoretical basis for developing wide-used effective HIV-1 vaccine. |
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