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Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.
Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro.
Afiliação
  • Nishiyama S; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Slack OA; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Lokugamage N; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Hill TE; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Juelich TL; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Zhang L; b Galveston National Laboratory, The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Smith JK; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Perez D; b Galveston National Laboratory, The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Gong B; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Freiberg AN; b Galveston National Laboratory, The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
  • Ikegami T; a Department of Pathology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
Virulence ; 7(8): 871-881, 2016 11 16.
Article em En | MEDLINE | ID: mdl-27248570
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Febre do Vale do Rift / Vacinas Virais / Proteínas não Estruturais Virais Limite: Animals / Humans Idioma: En Revista: Virulence Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Febre do Vale do Rift / Vacinas Virais / Proteínas não Estruturais Virais Limite: Animals / Humans Idioma: En Revista: Virulence Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos