UNSPECIFIED. (1999) Phenotypic consequences of rearranging the P, M, and G genes of vesicular stomatitis virus. JOURNAL OF VIROLOGY, 73 (6). pp. 4705-4712. ISSN 0022-538X

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Abstract

The nonsegmented negative-strand RNA viruses (order Mononegavirales) include many important human pathogens. The order of their genes, which is highly conserved, is the major determinant of the relative levels of gene expression, since genes that are close to the single promoter site at the 3' end of the viral genome are transcribed at higher levels than those that occupy more distal positions. We manipulated an infectious cDNA clone of the prototypic vesicular stomatitis virus (VSV) to rearrange three of the five viral genes, using an approach which left the viral nucleotide sequence otherwise unaltered. The central three genes in the gene order, which encode the phosphoprotein P, the matrix protein M, and the glycoprotein G, were rearranged into all six possible orders. Viable viruses were recovered from each of the rearranged cDNAs. The recovered viruses were examined for their levels of gene expression, growth potential in cell culture, and virulence in mice. Gene rearrangement changed the expression levels of the encoded proteins in concordance with their distance from the 3' promoter. Some of the viruses with rearranged genomes replicated as well or slightly better than wildtype virus in cultured cells, while others showed decreased replication. All of the viruses were lethal for mice, although the time to symptoms and death following inoculation varied. These data show that despite the highly conserved gene order of the Mononegavirales, gene rearrangement is not lethal or necessarily even detrimental to the virus. These findings suggest that the conservation of the gene order observed among the Mononegavirales may result from immobilization of the ancestral gene order due to the lack of a mechanism for homologous recombination in this group of viruses. As a consequence, gene rearrangement should be irreversible and provide an approach for constructing viruses with novel phenotypes.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology > QR355 Virology
Journal or Publication Title:	JOURNAL OF VIROLOGY
Publisher:	AMER SOC MICROBIOLOGY
ISSN:	0022-538X
Official Date:	June 1999
Dates:	Date Event June 1999 UNSPECIFIED
Volume:	73
Number:	6
Number of Pages:	8
Page Range:	pp. 4705-4712
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/14549

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