Rapid accumulation of virulent rift valley fever virus in mice from an attenuated virus carrying a single nucleotide substitution in the M RNA

John C. Morrill, Tetsuro Ikegami, Naoko Yoshikawa-Iwata, Nandadeva Lokugamage, Sungyong Won, Kaori Terasaki, Aya Zamoto-Niikura, C. J. Peters, Shinji Makino

Research output: Contribution to journalArticle

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Abstract

Background: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negativestranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates. Methodology/Principal Findings: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site. Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system. Intraperitoneal inoculation of rZH501-M847-A into mice caused a rapid and efficient viral accumulation in the sera, livers, spleens, kidneys and brains, and killed most of the mice within 8 days, whereas rZH501-M847-G caused low viremia titers, did not replicate as efficiently as did rZH501-M847-A in these organs, and had attenuated virulence to mice. Remarkably, as early as 2 days postinfection with rZH501-M847-G, the viruses carrying A at M847 emerged and became the major virus population thereafter, while replicating viruses retained the input A residue at M847 in rZH501-M847-A-infected mice. Conclusions/Significance: These data demonstrated that the single nucleotide substitution in the Gn protein substantially affected the RVFV mouse virulence and that a virus population carrying the virulent viral genotype quickly emerged and became the major viral population within a few days in mice that were inoculated with the attenuated virus

Original languageEnglish (US)
Article numbere9986
JournalPLoS One
Volume5
Issue number4
DOIs
StatePublished - 2010

Fingerprint

Rift Valley fever virus
Viruses
Substitution reactions
Nucleotides
nucleotides
RNA
viruses
mice
fever
Virulence
Phlebovirus
Fever
virulence
Bunyaviridae
Population
Viral Envelope Proteins
Reverse Genetics
abortion (animals)
Induced Abortion
Viremia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Rapid accumulation of virulent rift valley fever virus in mice from an attenuated virus carrying a single nucleotide substitution in the M RNA. / Morrill, John C.; Ikegami, Tetsuro; Yoshikawa-Iwata, Naoko; Lokugamage, Nandadeva; Won, Sungyong; Terasaki, Kaori; Zamoto-Niikura, Aya; Peters, C. J.; Makino, Shinji.

In: PLoS One, Vol. 5, No. 4, e9986, 2010.

Research output: Contribution to journalArticle

Morrill, John C. ; Ikegami, Tetsuro ; Yoshikawa-Iwata, Naoko ; Lokugamage, Nandadeva ; Won, Sungyong ; Terasaki, Kaori ; Zamoto-Niikura, Aya ; Peters, C. J. ; Makino, Shinji. / Rapid accumulation of virulent rift valley fever virus in mice from an attenuated virus carrying a single nucleotide substitution in the M RNA. In: PLoS One. 2010 ; Vol. 5, No. 4.
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abstract = "Background: Rift Valley fever virus (RVFV), a member of the genus Phlebovirus within the family Bunyaviridae, is a negativestranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, while in livestock it causes fever and high abortion rates. Methodology/Principal Findings: Sequence analysis showed that a wild-type RVFV ZH501 preparation consisted of two major viral subpopulations, with a single nucleotide heterogeneity at nucleotide 847 of M segment (M847); one had a G residue at M847 encoding glycine in a major viral envelope Gn protein, while the other carried A residue encoding glutamic acid at the corresponding site. Two ZH501-derived viruses, rZH501-M847-G and rZH501-M847-A, carried identical genomic sequences, except that the former and the latter had G and A, respectively, at M847 were recovered by using a reverse genetics system. Intraperitoneal inoculation of rZH501-M847-A into mice caused a rapid and efficient viral accumulation in the sera, livers, spleens, kidneys and brains, and killed most of the mice within 8 days, whereas rZH501-M847-G caused low viremia titers, did not replicate as efficiently as did rZH501-M847-A in these organs, and had attenuated virulence to mice. Remarkably, as early as 2 days postinfection with rZH501-M847-G, the viruses carrying A at M847 emerged and became the major virus population thereafter, while replicating viruses retained the input A residue at M847 in rZH501-M847-A-infected mice. Conclusions/Significance: These data demonstrated that the single nucleotide substitution in the Gn protein substantially affected the RVFV mouse virulence and that a virus population carrying the virulent viral genotype quickly emerged and became the major viral population within a few days in mice that were inoculated with the attenuated virus",
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T1 - Rapid accumulation of virulent rift valley fever virus in mice from an attenuated virus carrying a single nucleotide substitution in the M RNA

AU - Morrill, John C.

AU - Ikegami, Tetsuro

AU - Yoshikawa-Iwata, Naoko

AU - Lokugamage, Nandadeva

AU - Won, Sungyong

AU - Terasaki, Kaori

AU - Zamoto-Niikura, Aya

AU - Peters, C. J.

AU - Makino, Shinji

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