PDF(Pubmed)
Abstract：
PYHIN proteins are only found in mammals and play key roles in the defense against bacterial and viral pathogens. The corresponding gene locus shows variable deletion and expansion ranging from 0 genes in bats, over 1 in cows, and 4 in humans to a maximum of 13 in mice. While initially thought to act as cytosolic immune sensors that recognize foreign DNA, increasing evidence suggests that PYHIN proteins also inhibit viral pathogens by more direct mechanisms. Here, we examined the ability of all 13 murine PYHIN proteins to inhibit HIV-1 and murine leukemia virus (MLV). We show that overexpression of p203, p204, p205, p208, p209, p210, p211, and p212 strongly inhibits production of infectious HIV-1; p202, p207, and p213 had no significant effects, while p206 and p214 showed intermediate phenotypes. The inhibitory effects on infectious HIV-1 production correlated significantly with the suppression of reporter gene expression by a proviral Moloney MLV-eGFP construct and HIV-1 and Friend MLV LTR luciferase reporter constructs. Altogether, our data show that the antiretroviral activity of PYHIN proteins is conserved between men and mice and further support the key role of nuclear PYHIN proteins in innate antiviral immunity.
摘要：
PYHIN蛋白仅在哺乳动物中发现,并且在针对细菌和病毒病原体的防御中起关键作用。在蝙蝠中，相应的基因座显示出可变的缺失和扩展，范围从0个基因，奶牛超过1，人类为4，小鼠为13。虽然最初被认为是识别外源DNA的细胞溶质免疫传感器，越来越多的证据表明，PYHIN蛋白也通过更直接的机制抑制病毒病原体。这里,我们检测了所有13种鼠PYHIN蛋白抑制HIV-1和鼠白血病病毒(MLV)的能力.我们显示p203、p204、p205、p208、p209、p210、p211和p212的过表达强烈抑制感染性HIV-1的产生；p202、p207和p213没有显著影响，而p206和p214显示中间表型。对感染性HIV-1产生的抑制作用与前病毒MoloneyMLV-eGFP构建体以及HIV-1和FriendMLVLTR荧光素酶报告构建体对报告基因表达的抑制显着相关。总之,我们的数据表明，PYHIN蛋白的抗逆转录病毒活性在男性和小鼠之间是保守的，并进一步支持核PYHIN蛋白在先天抗病毒免疫中的关键作用。
