Coronavirus non-structural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines

R. Zust, L. Cervantes-Barragan, T. Kuri, Gjon Blakqori, F. Weber, B. Ludewig, V. Thiel

Research output: Contribution to journalArticlepeer-review

191 Citations (Scopus)

Abstract

Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.
Original languageEnglish
Article numbere109
JournalPLoS Pathogens
Volume3
Issue number8
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Attenuated viral vaccines
  • Coronavirus

Fingerprint

Dive into the research topics of 'Coronavirus non-structural protein 1 is a major pathogenicity factor: implications for the rational design of coronavirus vaccines'. Together they form a unique fingerprint.

Cite this