Pak A S, Everly D N, Knight K, Read G S
Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City 64110-2499, USA.
Virology. 1995 Aug 20;211(2):491-506. doi: 10.1006/viro.1995.1431.
The virion host shutoff (vhs) function of herpes simplex virus induces degradation of host mRNAs at early times and rapid turnover of viral mRNAs throughout infection. Previous studies have shown that disruption of the UL41 gene abrogates vhs activity, but have not determined whether the UL41 polypeptide is the direct inducer of mRNA degradation or whether it is the only virion component required for this activity. In this paper we report that transfection of cells with UL41 inhibits expression of a cotransfected CAT reporter gene and that the inhibition is not dependent upon other viral genes. Inhibition of CAT expression was due to UL41-dependent reduction of CAT mRNA levels. UL41 alleles encoding polypeptides that lacked vhs activity during virus infections exhibited a similar lack of activity in transfected cells. The results indicate that the UL41 polypeptide is the direct inducer of host mRNA degradation following virus infection and that it is the only virion component directly required for this activity. A 382-amino-acid nonsense polypeptide missing the last 107 residues of UL41 lacked inhibitory activity, but was packaged into virions, while a 343-amino-acid nonsense polypeptide lacked both inhibitory activity and the ability to be packaged.
单纯疱疹病毒的病毒体宿主关闭（vhs）功能在感染早期诱导宿主mRNA降解，并在整个感染过程中使病毒mRNA快速周转。先前的研究表明，UL41基因的破坏消除了vhs活性，但尚未确定UL41多肽是否是mRNA降解的直接诱导物，或者它是否是该活性所需的唯一病毒体成分。在本文中，我们报告用UL41转染细胞会抑制共转染的CAT报告基因的表达，并且这种抑制不依赖于其他病毒基因。CAT表达的抑制是由于UL41依赖性地降低了CAT mRNA水平。在病毒感染期间缺乏vhs活性的编码多肽的UL41等位基因在转染细胞中也表现出类似的活性缺乏。结果表明，UL41多肽是病毒感染后宿主mRNA降解的直接诱导物，并且它是该活性直接所需的唯一病毒体成分。缺少UL41最后107个残基的382个氨基酸的无义多肽缺乏抑制活性，但被包装到病毒体中，而343个氨基酸的无义多肽既缺乏抑制活性又缺乏被包装的能力。
