Inactivation of expression of gene 4 of mouse hepatitis virus strain JHM does not affect virulence in the murine CNS

E Ontiveros; L Kuo; P S Masters; S Perlman

doi:10.1006/viro.2001.1167

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Inactivation of expression of gene 4 of mouse hepatitis virus strain JHM does not affect virulence in the murine CNS

Journal article

Open access

Peer reviewed

Inactivation of expression of gene 4 of mouse hepatitis virus strain JHM does not affect virulence in the murine CNS

E Ontiveros, L Kuo, P S Masters and S Perlman

Virology, Vol.289(2), pp.230-238

10/25/2001

DOI: 10.1006/viro.2001.1167

PMID: 11689046

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Abstract

The protein encoded by ORF 4 of mouse hepatitis virus (MHV) is not required for growth of some strains in tissue culture cells, but its role in pathogenesis in the murine host has not been defined previously in a controlled manner. MHV strain JHM causes acute and chronic neurological diseases in susceptible strains of rodents. To genetically manipulate the structural proteins of this and other strains of MHV, we have generalized an interspecies-targeted RNA recombination selection that was originally developed for the A59 strain of MHV. Using this approach, a recombinant MHV-JHM was constructed in which gene 4 was genetically inactivated. Virus lacking gene 4 expression replicated in tissue culture cells with similar kinetics to recombinant virus in which gene 4 expression was not disrupted. Both types of viruses exhibited similar virulence when analyzed in a murine model of encephalitis. These results establish a targeted recombination system for inserting mutations into MHV-JHM. Furthermore, the protein encoded by ORF 4 is not essential for growth in tissue culture cells or in the CNS of the infected host.

Cell Line

Hippocampus - virology

Mutagenesis, Site-Directed

Mice, Inbred C57BL

Open Reading Frames

Virulence

Cerebral Cortex - virology

Male

Murine hepatitis virus - pathogenicity

Animals

Coronavirus Infections - virology

Time Factors

Recombination, Genetic

Genes, Viral

Mice

Central Nervous System - virology

Murine hepatitis virus - genetics

Details

Title: Subtitle: Inactivation of expression of gene 4 of mouse hepatitis virus strain JHM does not affect virulence in the murine CNS
Creators: E Ontiveros - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA
L Kuo
P S Masters
S Perlman
Resource Type: Journal article
Publication Details: Virology, Vol.289(2), pp.230-238
DOI: 10.1006/viro.2001.1167
PMID: 11689046
NLM abbreviation: Virology
ISSN: 0042-6822
eISSN: 1096-0341
Publisher: United States
Grant note: F31 AI10348 / NIAID NIH HHS NS 36592 / NINDS NIH HHS NS 40438 / NINDS NIH HHS AI 39544 / NIAID NIH HHS
Language: English
Date published: 10/25/2001
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777472702771

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