title: Interpatient mutational spectrum of human coronavirus-OC43 revealed by illumina sequencing.
abstract: Human coronaviruses (HCoV) are RNA viruses that cause respiratory tract infections with viral replication of limited duration. The host and viral population heterogeneity could influence clinical phenotypes. Employing long RT-PCR with Illumina sequencing, we quantified the gene mutation load at 0.5% mutation frequency for the 4529 bp-domain spanning the Spike gene (4086 bp) of HCoV-OC43 in four upper respiratory clinical specimens obtained during acute illness. There were a total of 121 mutations for all four HCoV samples with the average number of mutations at 30.3 ± 10.2, which is significantly higher than that expected from the Illumina sequencing error rate. There were two mutation peaks, one at the 5' end and the other near position 1 550 in the S1 subunit. Two coronavirus samples were genotype B and two were genotype D, clustering with HCoV-OC43 strain AY391777 in neighbor-joining tree phylogenetic analysis. Nonsynonymous mutations were 76.1 ± 14% of mutation load. Although lower than other RNA viruses such as hepatitis C virus, HCoV-OC43 did exhibit quasi-species. The rate of nonsynonymous mutations was higher in the HCoV-OC43 isolates than in hepatitis C (HCV) virus genotype 1a isolates analyzed for comparison in this study. These characteristics of HCoV-OC43 may affect viral replication dynamics, receptor binding, antigenicity, evolution, transmission, and clinical illness.
authors.affiliation: VA St. Louis Health Care System, St. Louis, Missouri.|Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Geoffrey J
authors.identifier: 0000-0003-4558-2713
authors.initials: GJ
authors.lastname: Gorse
authors.affiliation: VA St. Louis Health Care System, St. Louis, Missouri.|Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Gira B
authors.initials: GB
authors.lastname: Patel
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, Missouri.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Fan
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D016000:Cluster Analysis; D018352:Coronavirus Infections / Q000821:virology*; D028962:Coronavirus OC43, Human / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D064370:Spike Glycoprotein, Coronavirus / Q000235:genetics
chemical_list: D064370:Spike Glycoprotein, Coronavirus
keywords: coronavirus; genetic variability; genetic variation; hepatitis C virus; humoral immunity; mutation