Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus
Autor: | Daniel Janies, Xinsheng Zhang, David J. Spiro, Mustafa Hasöksüz, Nagesh Hadya, Rebecca A. Halpin, Shiliang Wang, Yuxin Tang, Elodie Ghedin, Sarah Stollar, Linda J. Saif |
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Rok vydání: | 2007 |
Předmět: |
040301 veterinary sciences
Molecular Sequence Data Virulence Genome Viral Biology Viral Nonstructural Proteins medicine.disease_cause Article 0403 veterinary science Complete genomic sequence 03 medical and health sciences Open Reading Frames Viral Envelope Proteins Virology medicine Amino Acid Sequence Porcine Respiratory Coronavirus Gene Tropism shift Tropism Phylogeny 030304 developmental biology Infectivity Alanine 0303 health sciences Mutation Membrane Glycoproteins Transmissible gastroenteritis virus Attenuation 04 agricultural and veterinary sciences Spike Glycoprotein Coronavirus biology.protein Antibody Sequence Alignment |
Zdroj: | Virology |
ISSN: | 0042-6822 |
DOI: | 10.1016/j.virol.2006.08.051 |
Popis: | Transmissible gastroenteritis virus (TGEV) isolates that have been adapted to passage in cell culture maintain their infectivity in vitro but may lose their pathogenicity in vivo. To better understand the genomic mechanisms for viral attenuation, we sequenced the complete genomes of two virulent TGEV strains and their attenuated counterparts: virulent TGEV Miller M6 and attenuated TGEV Miller M60 and virulent TGEV Purdue and attenuated TGEV Purdue P115, together with the ISU-1 strain of porcine respiratory coronavirus (PRCV-ISU-1), a naturally occurring TGEV deletion mutant with an altered respiratory tropism and reduced virulence. Pairwise comparison at both the nucleotide (nt) and amino acid (aa) levels between virulent and attenuated TGEV strains identified a common change in nt 1753 of the spike gene, resulting in a serine to alanine mutation at aa position 585 of the spike proteins of the attenuated TGEV strains. Alanine was also present in this protein in PRCV-ISU-1. Particularly noteworthy, the serine to alanine mutation resides in the region of the major antigenic site A/B (aa 506–706) that elicits neutralizing antibodies and within the domain mediating the cell surface receptor aminopeptidase N binding (aa 522–744). Comparison of the predicted polypeptide products of ORF3b showed significant deletions in the naturally attenuated PRCV-ISU-1 and TGEV Miller M60; these deletions occurred at a common break point, suggesting a related mechanism of recombination that may affect viral virulence or tropism. Sequence comparisons at both genomic and protein levels indicated that PRCV-ISU-1 had a closer relationship with TGEV Miller strains than Purdue strains. Phylogenetic analyses showed that virulence is an evolutionarily labile trait in TGEV and that TGEV strains as a group share a common ancestor with PRCV. |
Databáze: | OpenAIRE |
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