Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, Maharashtra, India.
Savitribai Phule Pune University, Pune 411007, Maharashtra, India.
Viruses. 2021 Jul 23;13(8):1432. doi: 10.3390/v13081432.
Antisense protein of Human T-cell Leukemia Virus Type 2 (HTLV-2), also called APH-2, negatively regulates the HTLV-2 and helps the virus to maintain latency via scheming the transcription. Despite the remarkable occurrence of HTLV-2/HIV-1 co-infection, the role of APH-2 influencing HIV-1 replication kinetics is poorly understood and needs investigation. In this study, we investigated the plausible role of APH-2 regulating HIV-1 replication. Herein, we report that the overexpression of APH-2 not only hampered the release of HIV-1 pNL4.3 from 293T cells in a dose-dependent manner but also affected the cellular gag expression. A similar and consistent effect of APH-2 overexpression was also observed in case of HIV-1 gag expression vector HXB2 pGag-EGFP. APH-2 overexpression also inhibited the ability of HIV-1 Tat to transactivate the HIV-1 LTR-driven expression of luciferase. Furthermore, the introduction of mutations in the IXXLL motif at the N-terminal domain of APH-2 reverted the inhibitory effect on HIV-1 Tat-mediated transcription, suggesting the possible role of this motif towards the downregulation of Tat-mediated transactivation. Overall, these findings indicate that the HTLV-2 APH-2 may affect the HIV-1 replication at multiple levels by (a) inhibiting the Tat-mediated transactivation and (b) hampering the virus release by affecting the cellular gag expression.
人类 T 细胞白血病病毒 2 型（HTLV-2）的反义蛋白，也称为 APH-2，通过设计转录来负调控 HTLV-2 并帮助病毒维持潜伏期。尽管 HTLV-2/HIV-1 合并感染的发生率很高，但 APH-2 影响 HIV-1 复制动力学的作用仍知之甚少，需要进一步研究。在这项研究中，我们研究了 APH-2 调节 HIV-1 复制的可能作用。在此，我们报告 APH-2 的过表达不仅以剂量依赖的方式阻碍了 293T 细胞中 HIV-1 pNL4.3 的释放，而且还影响了细胞 gag 表达。在 HIV-1 gag 表达载体 HXB2 pGag-EGFP 的情况下，也观察到 APH-2 过表达的类似和一致的效果。APH-2 过表达还抑制了 HIV-1 Tat 转激活 HIV-1 LTR 驱动的荧光素酶表达的能力。此外，在 APH-2 氨基末端结构域中的 IXXLL 基序中引入突变，逆转了对 HIV-1 Tat 介导转录的抑制作用，表明该基序可能在下调 Tat 介导的转激活中起作用。总之，这些发现表明 HTLV-2 APH-2 可能通过 (a) 抑制 Tat 介导的转激活和 (b) 通过影响细胞 gag 表达来阻碍病毒释放，从而在多个水平上影响 HIV-1 复制。
