Human Respiratory Coronavirus OC43: Genetic Stability and Neuroinvasion
Open Access
- 15 August 2004
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 78 (16) , 8824-8834
- https://doi.org/10.1128/jvi.78.16.8824-8834.2004
Abstract
The complete genome sequences of the human coronavirus OC43 (HCoV-OC43) laboratory strain from the American Type Culture Collection (ATCC), and a HCoV-OC43 clinical isolate, designated Paris, were obtained. Both genomes are 30,713 nucleotides long, excluding the poly(A) tail, and only differ by 6 nucleotides. These six mutations are scattered throughout the genome and give rise to only two amino acid substitutions: one in the spike protein gene (I958F) and the other in the nucleocapsid protein gene (V81A). Furthermore, the two variants were shown to reach the central nervous system (CNS) after intranasal inoculation in BALB/c mice, demonstrating neuroinvasive properties. Even though the ATCC strain could penetrate the CNS more effectively than the Paris 2001 isolate, these results suggest that intrinsic neuroinvasive properties already existed for the HCoV-OC43 ATCC human respiratory isolate from the 1960s before it was propagated in newborn mouse brains. It also demonstrates that the molecular structure of HCoV-OC43 is very stable in the environment (the two variants were isolated ca. 40 years apart) despite virus shedding and chances of persistence in the host. The genomes of the two HCoV-OC43 variants display 71, 53.1, and 51.2% identity with those of mouse hepatitis virus A59, severe acute respiratory syndrome human coronavirus Tor2 strain (SARS-HCoV Tor2), and human coronavirus 229E (HCoV-229E), respectively. HCoV-OC43 also possesses well-conserved motifs with regard to the genome sequence of the SARS-HCoV Tor2, especially in open reading frame 1b. These results suggest that HCoV-OC43 and SARS-HCoV may share several important functional properties and that HCoV-OC43 may be used as a model to study the biology of SARS-HCoV without the need for level three biological facilities.Keywords
This publication has 90 references indexed in Scilit:
- Translation of the Minor Capsid Protein of a Calicivirus Is Initiated by a Novel Termination-dependent Reinitiation MechanismJournal of Biological Chemistry, 2003
- The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core ComplexJournal of Virology, 2003
- Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 LineagePublished by Elsevier ,2003
- The Genome Sequence of the SARS-Associated CoronavirusScience, 2003
- Interaction of the Coronavirus Nucleoprotein with Nucleolar Antigens and the Host CellJournal of Virology, 2002
- Downstream Sequences Influence the Choice between a Naturally Occurring Noncanonical and Closely Positioned Upstream Canonical Heptameric Fusion Motif during Bovine Coronavirus Subgenomic mRNA SynthesisJournal of Virology, 2001
- Structural and functional analysis of the S proteins of two human coronavirus OC43 strains adapted to growth in different cellsArchiv für die gesamte Virusforschung, 1996
- Sequence and expression of the ns2 protein gene of human coronavirus OC43Journal of General Virology, 1995
- Human coronavirus gene expression in the brains of multiple sclerosis patientsVirology, 1992
- Sequence analysis of nucleocapsid gene and leader RNA of human coronavirus OC43Virus Research, 1989