The U(L)41 protein of herpes simplex virus 1 degrades RNA by endonucleolytic cleavage in absence of other cellular or viral proteins.
نویسندگان
چکیده
The herpes simplex virus 1 ORF U(L)41 encodes a protein (virion host shutoff or vhs) associated with selective degradation of mRNA early in infection. Some mRNAs, exemplified by GAPDH or beta-actin mRNAs, are degraded rapidly. Others, for example IEX-1 mRNA, are degraded in two stages: whereas the 3' domain disappears rapidly, a large 5' domain fragment of the mRNA lingers for several hours. Still a third, exemplified by tristetraprolin mRNA, is not degraded, allowing its protein product to accumulate in infected cells. Here we report the following: (i) a GST-vhs protein produced in Escherichia coli, solubilized and purified to homogeneity acts as bona fide endoribonuclease when tested on in vitro transcribed IEX-1 probes. A GST-vhs protein in which three key vhs amino acids were replaced with alanines, solubilized and purified by the same protocol, had no enzymatic activity. (ii) The number of fragments generated by cleavage of a truncated IEX-1 RNA by vhs appears to be small; the cleavage sites are centered at or near the AU-rich elements located at the 3' untranslated region of the mRNA. A truncated RNA containing only the IEX-1 coding domain was cleaved numerous times. (iii) In cells infected at high multiplicity and exposed to a large number of particles per cell, the vhs protein accumulated within 3 h after infection, in small uniform cytoplasmic granules raising the possibility that vhs colocalizes with tristerapolin, a protein induced after infection, in structures involved in degradation of RNA.
منابع مشابه
Post-transcriptional processing of cellular RNAs in herpes simplex virus-infected cells.
In HSV-1 (herpes simplex virus 1)-infected cells, the U(L)41 gene product carried with the virion has been shown to mediate the degradation of mRNA, leading to the shut-off of cellular protein synthesis. Analysis of the RNAs accumulating in cells infected with HSV-1 revealed the accumulation of RNAs encoding numerous cellular proteins both associated with and independent of activation of the NF...
متن کاملThe Effect of Herpes Simplex Virus Virion Host Shutoff Gene- a New Suicide Gene- on Tumor Cells
Background: The herpes simplex virus (HSV) UL41 gene product, virion host shutoff (Vhs) protein, mediates the rapid degradation of both viral and cellular mRNA. This ability suggests that Vhs protein can be used as a suicide gene in cancer gene therapy applications. The recent reports have shown that the degradation of cellular mRNA during herpes simplex infection is selective. RNA containing A...
متن کاملExpression and in vitro Characterization of Herpes Simplex Virus 1 (HSV-1) ORF P Protein
Herpes simplex virus 1 (HSV-1) unspliced 8.3 latency associated transcript (LAT), which located in the long repeat sequences, has been shown to contain at least 16 open reading frames (ORF: A-P). One of these ORF, ORF P, maps almost entirely antisense to HSV-1 neurovirulence gene, ICP34.5. Both ORF P and ICP34.5 are located in the long repeat and are antisense overlapping genes. Therefore, in O...
متن کاملThe US3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins.
Earlier studies have shown that the d120 mutant of herpes simplex virus 1, which lacks both copies of the alpha4 gene, induces apoptosis in all cell lines tested. In some cell lines d120-induced apoptosis, manifested by the release of cytochrome c, activation of caspase 3, and fragmentation of cellular DNA, is blocked by the overexpression of Bcl-2. In these cells viral protein kinase U(S)3 del...
متن کاملExpression of the Herpes Simplex Virus Type 2 Glycoprotein D in Baculovirus Expression System and Evaluation of Its Immunogenicity in Guinea Pigs
Background: Herpes simplex virus type 2 (HSV-2) is highly prevalent and major cause of genital herpes in humans. The life-long nature of infection and the increasing prevalence of genital herpes imply that vaccination is the best strategy for controlling the spread of infection and limiting HSV disease. HSV glycoprotein D (gD) is one of the most important viral immunogen which has an essential ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 103 8 شماره
صفحات -
تاریخ انتشار 2006