Document Detail


Attenuation of bunyamwera orthobunyavirus replication by targeted mutagenesis of genomic untranslated regions and creation of viable viruses with minimal genome segments.
MedLine Citation:
PMID:  23035233     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bunyamwera virus (BUNV) is the prototype virus for both the genus Orthobunyavirus and the family Bunyaviridae. BUNV has a tripartite, negative-sense RNA genome. The coding region of each segment is flanked by untranslated regions (UTRs) that are partially complementary. The UTRs play an important role in the virus life cycle by promoting transcription, replication, and encapsidation of the viral genome. Using reverse genetics, we generated recombinant viruses that contained deletions within the 3' and/or 5' UTRs of the L or M segments to determine the minimal UTRs competent for virus viability. We then generated viruses carrying deleted UTRs in all three segments. These viruses were grossly attenuated in tissue culture, being significantly impaired in their ability to produce plaques in BHK cells, and had a reduced capacity to cause host cell protein shutoff. After serial passage in tissue culture, some viruses partially recovered fitness, generating higher titers and producing larger plaques. We determined the complete nucleotide sequence for each virus. The deleted UTR sequences were maintained, and no amino acid changes were observed in the nonstructural proteins (NSs and NSm), the nucleocapsid protein (N), or the Gn glycoprotein. One virus had a single amino acid substitution in Gc. Three viruses contained amino acid changes in the viral polymerase that mostly occurred in the C-terminal domain of the L protein. Although the role of this domain remains unknown, we suggest that those changes might be involved in the evolution of the polymerase to recognize the deleted UTRs more efficiently.
Authors:
Béryl Mazel-Sanchez; Richard M Elliott
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Journal of virology     Volume:  86     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-01-28     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13672-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bunyamwera virus / genetics,  physiology*
Cell Line
Cricetinae
Genome, Viral*
Mutagenesis
Serial Passage
Untranslated Regions*
Virus Replication*
Grant Support
ID/Acronym/Agency:
G0800161//Medical Research Council; //Biotechnology and Biological Sciences Research Council; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Untranslated Regions
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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