The Varicella-Zoster Virus ORFS/L (ORF0) Gene Is Required for Efficient Viral Replication and Contains an Element Involved in DNA Cleavage
- 15 November 2010
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (22), 11661-11669
- https://doi.org/10.1128/jvi.00878-10
Abstract
The genome of varicella-zoster virus (VZV), a human alphaherpesvirus, consists of two unique regions, unique long (U L ) and unique short (U S ), each of which is flanked by inverted repeats. During replication, four isomers of the viral DNA are generated which are distinguished by the relative orientations of U L and U S . VZV virions predominantly package two isomeric forms of the genome that have a fixed orientation of U L . An open reading frame (ORF) of unknown function, ORFS/L, also referred to as ORF0, is located at the extreme terminus of U L , directly adjacent to the a -like sequences, which are known to be involved in cleavage and packaging of viral DNA. We demonstrate here that the ORFS/L protein localizes to the Golgi network in infected and transfected cells. Furthermore, we were able to demonstrate that deletion of the predicted ORFS/L gene is lethal, while retention of the N-terminal 28 amino acid residues resulted in viable yet replication-impaired virus. The growth defect was only partially attributable to the expression of the ORFS/L product, suggesting that the 5′ region of ORFS/L contains a sequence element crucial for cleavage/packaging of viral DNA. Consequently, mutations introduced into the extreme 5′ terminus of ORFS/L resulted in a defect in DNA cleavage, indicating that the region is indeed involved in the processing of viral DNA. Since the sequence element has no counterpart at the other end of U L , we concluded that our results can provide an explanation for the almost exclusive orientation of the U L seen in packaged VZV DNA.Keywords
This publication has 25 references indexed in Scilit:
- Herpesvirus systematicsVeterinary Microbiology, 2010
- Herpes simplex virus type 2 tegument protein UL56 relocalizes ubiquitin ligase Nedd4 and has a role in transport and/or release of virionsVirology Journal, 2009
- Herpes Simplex Virus Type 2 UL56 Interacts with the Ubiquitin Ligase Nedd4 and Increases Its UbiquitinationJournal of Virology, 2008
- A Self-Excisable Infectious Bacterial Artificial Chromosome Clone of Varicella-Zoster Virus Allows Analysis of the Essential Tegument Protein Encoded by ORF9Journal of Virology, 2007
- Genetic Analysis of Varicella-Zoster Virus ORF0 to ORF4 by Use of a Novel Luciferase Bacterial Artificial Chromosome SystemJournal of Virology, 2007
- Comparative analysis of the genomesPublished by Cambridge University Press (CUP) ,2007
- Complete, Annotated Sequence of the Pseudorabies Virus GenomeJournal of Virology, 2004
- Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral intraperitoneal pathogenicity to immunocompetent miceArchiv für die gesamte Virusforschung, 1994
- Identification and mapping of the UL56 gene transcript of herpes simplex virus type 1Virus Research, 1991
- Structure of the Genome Termini of Varicella-Zoster VirusJournal of General Virology, 1984