Paramyxovirus-based producton of Rift Valley fever virus replicon particles

P.J. Wichgers Schreur, N. Oreshkova, F. Harders, A. Bossers, R.J.M. Moormann, J.A. Kortekaas

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4 Citations (Scopus)

Abstract

Replicon-particle-based vaccines combine the efficacy of live-attenuated vaccines with the safety of inactivated or subunit vaccines. Recently, we developed Rift Valley fever virus (RVFV) replicon particles, also known as nonspreading RVFV (NSR), and demonstrated that a single vaccination with these particles can confer sterile immunity in target animals. NSR particles can be produced by transfection of replicon cells, which stably maintain replicating RVFV S and L genome segments, with an expression plasmid encoding the RVFV glycoproteins, Gn and Gc, normally encoded by the M-genome segment. Here, we explored the possibility to produce NSR with the use of a helper virus. We show that replicon cells infected with a Newcastle disease virus expressing Gn and Gc (NDV-GnGc) were able to produce high levels of NSR particles. In addition, using reverse genetics and site-directed mutagenesis, we were able to create an NDV-GnGc variant that lacks the NDV fusion protein and contains two amino acid substitutions in, respectively, Gn and HN. The resulting virus uses a unique entry pathway that facilitates the efficient production of NSR in a one-component system. The novel system provides a promising alternative for transfection-based NSR production.
Original languageEnglish
Pages (from-to)2638-2648
JournalJournal of General Virology
Volume95
Issue number12
DOIs
Publication statusPublished - 2014

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Keywords

  • newcastle-disease virus
  • hemagglutinin-neuraminidase protein
  • fusion protein
  • vaccine vector
  • nsm protein
  • hn protein
  • virulence
  • transcription
  • bunyaviridae
  • expression

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