Document Detail


Genetic subpopulations of Rift Valley fever virus strains ZH548 and MP-12 and recombinant MP-12 strains.
MedLine Citation:
PMID:  23035230     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments were responsible for attenuation, while the MP-12 S segment still encoded a virulent phenotype. We performed high-throughput sequencing of MP-12 vaccine, ZH548, and recombinant MP-12 (rMP-12) viruses. We found that rMP-12 contains very low numbers of viral subpopulations, while MP-12 and ZH548 contain 2 to 4 times more viral genetic subpopulations than rMP-12. MP-12 genetic subpopulations did not encode the ZH548 sequence at the 23 MP-12 consensus mutations. On the other hand, 4 and 2 mutations in M and L segments of MP-12 were found in ZH548 subpopulations. Thus, those 6 mutations were no longer MP-12-specific mutations. ZH548 encoded several unique mutations compared to other Egyptian strains, i.e., strains ZH501, ZH1776, and ZS6365. ZH548 subpopulations shared nucleotides at the mutation site common with those in the Egyptian strains, while MP-12 subpopulations did not share those nucleotides. Thus, MP-12 retains unique genetic subpopulations and has no evidence of reversion to the ZH548 sequence in the subpopulations. This study provides the first information regarding the genetic subpopulations of RVFV and shows the genetic stability of the MP-12 vaccine manufactured in MRC-5 cells.
Authors:
Nandadeva Lokugamage; Alexander N Freiberg; John C Morrill; Tetsuro Ikegami
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; 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:  2013-09-09    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13566-75     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cricetinae
Genes, Viral
Mutation
Polymerase Chain Reaction
Recombination, Genetic*
Rift Valley fever virus / classification,  genetics*
Grant Support
ID/Acronym/Agency:
R01 AI087643/AI/NIAID NIH HHS; R01 AI08764301-A1/AI/NIAID NIH HHS
Comments/Corrections

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


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