School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, China.
Front Immunol. 2022 Apr 5;13:850719. doi: 10.3389/fimmu.2022.850719. eCollection 2022.
HIV-1 CRF07_BC-p6Δ7, a strain with a seven amino acid deletion in the p6 region of the Gag protein, is becoming the dominant strain of HIV transmission among men who have sex with men (MSM) in China. Previous studies demonstrated that HIV-1 patients infected by CRF07_BC-p6Δ7 strain had lower viral load and slower disease progression than those patients infected with CRF07_BC wild-type strain. However, the underlying mechanism for this observation is not fully clarified yet. In this study, we constructed the recombinant DNA plasmid and adenovirus type 2 (Ad2) vector-based constructs to express the HIV-1 CRF07_BC Gag antigen with or without p6Δ7 mutation and then investigated their immunogenicity in mice. Our results showed that HIV-1 CRF07_BC Gag antigen with p6Δ7 mutation induced a comparable level of Gag-specific antibodies but stronger CD4 and CD8 T-cell immune responses than that of CRF07_BC Gag (07_BC-wt). Furthermore, we identified a series of T-cell epitopes, which induced strong T-cell immune response and cross-immunity with CRF01_AE Gag. These findings implied that the p6 protein with a seven amino acid deletion might enhance the Gag immunogenicity in particular cellular immunity, which provides valuable information to clarify the pathogenic mechanism of HIV-1 CRF07_BC-p6Δ7 and to develop precise vaccine strategies against HIV-1 infection.
HIV-1 CRF07_BC-p6Δ7,一种在 Gag 蛋白 p6 区域缺失七个氨基酸的毒株,正在成为中国男男性行为人群中 HIV 传播的主要毒株。先前的研究表明,感染 CRF07_BC-p6Δ7 株的 HIV-1 患者的病毒载量较低,疾病进展较慢,而感染 CRF07_BC 野生型株的患者则相反。然而,这种观察结果的潜在机制尚未完全阐明。在本研究中,我们构建了重组 DNA 质粒和腺病毒 2 型(Ad2)载体构建体,以表达具有或不具有 p6Δ7 突变的 HIV-1 CRF07_BC Gag 抗原,然后在小鼠中研究了它们的免疫原性。我们的结果表明,具有 p6Δ7 突变的 HIV-1 CRF07_BC Gag 抗原诱导了相当水平的 Gag 特异性抗体,但比 CRF07_BC Gag(07_BC-wt)更强的 CD4 和 CD8 T 细胞免疫反应。此外,我们鉴定了一系列 T 细胞表位,这些表位诱导了强烈的 T 细胞免疫反应和与 CRF01_AE Gag 的交叉免疫反应。这些发现表明,具有七个氨基酸缺失的 p6 蛋白可能增强了 Gag 的免疫原性,特别是细胞免疫,这为阐明 HIV-1 CRF07_BC-p6Δ7 的发病机制和开发针对 HIV-1 感染的精确疫苗策略提供了有价值的信息。