Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR

Shoko Nishiyama, Olga A L Slack, Nandadeva Lokugamage, Terence E. Hill, Terry L. Juelich, Lihong Zhang, Jennifer K. Smith, David Perez, Bin Gong, Alexander Freiberg, Tetsuro Ikegami

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalVirulence
DOIs
StateAccepted/In press - Jun 16 2016

Keywords

  • attenuation
  • NSs
  • phlebovirus
  • PKR
  • punta toro virus
  • Rift valley fever virus
  • sandfly fever Sicilian virus
  • Toscana virus
  • vaccine

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology
  • Parasitology
  • Immunology
  • Microbiology (medical)

Fingerprint Dive into the research topics of 'Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR'. Together they form a unique fingerprint.

  • Cite this