Multifactorial role of HIV-Vpr in cell apoptosis revealed by a naturally truncated 54aa variant

作者：Ling Du, Cuisong Wu, Jun Sun, Tong Yu, Pan-Pan Lyu, San-Feng Han, Chao Qiu, Zhefeng Meng · 发表于：Chinese Medical Journal · 年份：2020 · DOI：10.1097/cm9.0000000000001297 · 被引用次数：2 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Hepatitis B Virus Studies

Although antiretroviral therapy (ART) is effective at suppressing the human immunodeficiency virus type 1 (HIV-1) replication, HIV-1 infection is still a global public health problem. HIV-1 accessory protein viral protein R (Vpr) is a multifunctional protein with a primary role in regulating cellular apoptosis.[1] The amino acid (aa) positions 52–96 in the C-terminus of Vpr were identified as the apoptosis-regulating domain.[2,3] In this study, we found a natural Vpr variant truncated at the 54 aa position (∗54Vpr) from HIV patients in the acquired immune deficiency syndrome (AIDS) phase that mediated both pro- and antiapoptotic cellular effects by interacting with distinct adenine nucleotide translocator (ANT) isoforms. A novel apoptosis-regulating domain was further identified in the 23–37 aa position in the N-terminus of Vpr. The truncated CRF07_BC ∗54Vpr and intact Vpr (XJN0084_54W) were from the previously described XJN0084 isolate,[4] while the B subtype ∗54Vpr (pNL4-3_54Stop) and the wildtype Vpr were from pNL4-3 [Figure 1A]. The full-length gene-encoding region for ANT1–3 was amplified using the following primers: ANT1-F: 5’-CCCGAATTCTCACCATGGGTGATCAC GCTTGG-3’, ANT1-R: 5’-AGAAAGCTTGACATATTTTTTGATCTCAT-3’; ANT2-F: 5’-CCCGAATTCTCACCATGACAGATGCCGCTGTG-3’, ANT2-R: 5’-AGA AAGCTTTGTGTACTTCTTGATTTCAT; ANT3-F: 5’-CCCGAATTCTCACC ATGACGGAACAGGCCATC-3’, ANT3-R: 5’-AGAAAGCTTGATCACCTTCTTGAGCTCGT-3’. Green fluorescent protein (GFP)-Vpr expression vectors were constructed using the...