Submitted to: Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/21/2007
Publication Date: 9/29/2007
Citation: Fernandez-Sainz, I., Holinka, L.G., Lu, Z., Risatti, G.R., Borca, M.V. 2007. Removal of a N-linked Glycosylation Site on the Classical Swine Fever Virus Strain Brescia E(rns) Glycoprotein Affects Virulence in Swine. Virology. 370:122-129. Interpretive Summary: Classical Swine Fever Virus (CSFV) E(rns) glycoprotein is the most important of the four structural proteins. This glycoprotein has been involved in diverse virus functions, including virus attachment and entry to target cells during infection as well as the induction of protective immune response during vaccination. E(rns) is a glycosylated protein, although the role of this glycosylation in the biology of the virus is completely unknown. In this report, we analyzed the function of the glycosylation of E(rns) in the capacity of the virus to induce disease in swine. We showed that a mutated virus, containing partial elimination of the glycosylation in E(rns) showed attenuation in swine. This mutated virus, although attenuated, is able to induce a strong immune response in the infected animals. This resulted in protection against challenge as early as 3 days post infection with the virus mutant. Thus, this newly developed virus could potentially be the basis for a live attenuated vaccine against CSFV.
Technical Abstract: Classical Swine Fever Virus (CSFV) E(rns) glycoprotein is involved in several functions; including virus attachment and entry to target cells, production of antibodies, and virulence. Here, we describe the role of CSFV strain Brescia E(rns) glycosylation on virulence in swine. Amino acid residue N to A substitutions of putative E(rns) glycosylation sites resulted in seven single-site mutant viruses. The N269A substitution rendered an attenuated virus (N1 virus) that, unlike BIC virus and other mutants, produced a transient infection in swine characterized by decreased virus replication and shedding. N1 virus efficacious protection of swine demonstrates that residue N269 could be modified for development of CSF live-attenuated vaccines.