The Role of the PKR-Inhibitory Genes, E3L and K3L, in Determining Vaccinia Virus Host Range

Vaccinia virus encodes two regulators of the cellular antiviral response. The E3L gene is thought to act primarily by sequestering double-stranded RNA, whereas the K3L gene is thought to act as a competitive inhibitor of the double-stranded RNA-dependent protein kinase, PKR. The broad host range ass...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2002-07, Vol.299 (1), p.133-141
Main Authors: Langland, Jeffrey O., Jacobs, Bertram L.
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cricetinae
dsRNA
E3L
eIF-2 Kinase - antagonists & inhibitors
eIF-2 Kinase - metabolism
HeLa Cells
host range
Humans
interferon
K3L
PKR
RNA, Double-Stranded - biosynthesis
RNA-Binding Proteins - genetics
RNA-Binding Proteins - physiology
vaccinia virus
Vaccinia virus - genetics
Vaccinia virus - physiology
Viral Proteins - genetics
Viral Proteins - physiology
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Vaccinia virus encodes two regulators of the cellular antiviral response. The E3L gene is thought to act primarily by sequestering double-stranded RNA, whereas the K3L gene is thought to act as a competitive inhibitor of the double-stranded RNA-dependent protein kinase, PKR. The broad host range associated with vaccinia virus replication appears to be related to the presence of these genes. The E3L gene is required for replication in HeLa cells, but is not required for replication in BHK cells. On the contrary, the K3L gene is required for replication in BHK cells, but is dispensable for replication in HeLa cells. Our results suggest that these cell lines varied in the expression of endogenous activatable PKR and that replication of vaccinia virus in different cell lines led to altered levels of double-stranded RNA synthesis from the virus. Vaccinia virus was able to overcome these cellular variations by regulating PKR activity through the synthesis of either E3L or K3L. The results suggest that vaccinia virus has evolved a broad host range by maintaining both the E3L and the K3L genes.
ISSN:0042-6822
1096-0341
DOI:10.1006/viro.2002.1479