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Analysis of nonessential gene function in recombinant MHV-JHM: Gene 4 knockout recombinant virus
Book chapter   Peer reviewed

Analysis of nonessential gene function in recombinant MHV-JHM: Gene 4 knockout recombinant virus

Evelena Ontiveros, Lili Kuo, Paul Masters and Stanley Perlman
The Nidoviruses, Vol.494, pp.83-89
Advances in experimental medicine and biology, 494, Springer
2001
DOI: 10.1007/978-1-4615-1325-4_13
PMID: 11774550

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Abstract

The large size of the Coronavirus genome has made reverse genetics difficult. Targeted recombination, a technique developed by Masters and colleagues, has facilitated the introduction of mutations into the Coronavirus genome (Kuo et al., 2000). Previous work by Skinner and Siddell showed that MHV-JHM ORF 4 encodes a 15 kDa protein composed of 139 amino acids. This protein is relatively rich in threonines and includes a hydrophobic region. The N-terminus contains a potential membrane-anchoring region and the C-terminus has a possible RNA binding region (Skinner and Siddell, 1985). MHV-S, a natural variant, does not encode a functional ORF 4 suggesting that the ORF 4 product was not necessary for growth in tissue culture cells or animals. Additionally this strain contained a deletion within ORF 5a (Yokomori and Lai, 1991). Lack of mRNA 4 synthesis most likely resulted from a point mutation in the intergenic sequence (UCUAAAC to UUUAAAC). In this study, targeted recombination was used to genetically disrupt ORF 4. This recombinant virus was then analyzed in a murine model of encephalitis.
Encephalomyelitis - virology Mice, Inbred C57BL Virulence Brain - virology Viral Proteins - genetics Lethal Dose 50 Murine hepatitis virus - pathogenicity Viral Proteins - metabolism Ecthyma, Contagious - metabolism Animals Coronavirus Infections - virology Recombination, Genetic Ecthyma, Contagious - genetics Gene Deletion Genes, Viral Mice Murine hepatitis virus - genetics Disease Models, Animal

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