Pivaris BioScience GmbH, 1030 Vienna, Austria.
Int J Mol Sci. 2022 Jun 29;23(13):7246. doi: 10.3390/ijms23137246.
The effect of the antiviral peptide TAT-I24 on viral gene expression in cells infected with murine cytomegalovirus (MCMV) was investigated. The expression of immediate-early, early and late genes was highly induced upon infection with MCMV. In the presence of the peptide, the expression of all tested genes was sustainably reduced to a similar extent, independent of whether they were immediate-early, early or late genes. In contrast, the expression of host genes, such as NF-κB inhibitor alpha (), interferon-induced protein with tetratricopeptide repeats 1 (), chemokine (C-X-C motif) ligand 10 (), chemokine (C-C motif) ligand 7 () and chemokine (C-C motif) ligand 5 (), which are induced early upon virus infection, was only transiently suppressed in peptide-treated cells. The expression of other host genes which are affected by MCMV infection and play a role in endoplasmic reticulum stress or DNA-damage repair was not inhibited by the peptide. A combination of TAT-I24 with the nucleoside analogue cidofovir showed enhancement of the antiviral effect, demonstrating that viral replication can be more efficiently inhibited with a combination of drugs acting at different stages of the viral life-cycle.
研究了抗病毒肽 TAT-I24 对感染鼠巨细胞病毒 (MCMV) 的细胞中病毒基因表达的影响。感染 MCMV 后，立即早期、早期和晚期基因的表达被高度诱导。在肽的存在下，所有测试基因的表达都被持续降低到相似的程度，无论它们是立即早期、早期还是晚期基因。相比之下，宿主基因的表达，如 NF-κB 抑制剂 alpha ()、干扰素诱导的具有四肽重复的蛋白 1 ()、趋化因子 (C-X-C 基序) 配体 10 ()、趋化因子 (C-C 基序) 配体 7 () 和趋化因子 (C-C 基序) 配体 5 ()，这些基因在病毒感染后早期被诱导，仅在肽处理的细胞中被短暂抑制。其他受 MCMV 感染影响并在内质网应激或 DNA 损伤修复中发挥作用的宿主基因的表达不受肽的抑制。TAT-I24 与核苷类似物更昔洛韦的联合使用增强了抗病毒作用，表明通过作用于病毒生命周期不同阶段的药物联合使用可以更有效地抑制病毒复制。
