Genetic subpopulations of rift valley fever virus strains ZH548 and MP-12 and recombinant MP-12 strains

Nandadeva Lokugamage, Alexander Freiberg, John C. Morrill, Tetsuro Ikegami

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 theMand 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 inMand 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.

Original languageEnglish (US)
Pages (from-to)13566-13575
Number of pages10
JournalJournal of Virology
Volume86
Issue number24
DOIs
StatePublished - Dec 2012

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Rift Valley fever virus
mutation
Mutation
Nucleotides
nucleotides
vaccines
Serial Passage
microbial genetics
fluorouracil
Synthetic Vaccines
genetic stability
Mutagens
Fluorouracil
Vaccines
cells
Viruses
Phenotype
phenotype
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Genetic subpopulations of rift valley fever virus strains ZH548 and MP-12 and recombinant MP-12 strains. / Lokugamage, Nandadeva; Freiberg, Alexander; Morrill, John C.; Ikegami, Tetsuro.

In: Journal of Virology, Vol. 86, No. 24, 12.2012, p. 13566-13575.

Research output: Contribution to journalArticle

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