Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate.
Group B coxsackieviruses (CVB) cause numerous diseases, including myocarditis, pancreatitis, aseptic meningitis and possibly type 1 diabetes. To date, infectious cDNA copies of CVB type 3 (CVB3) genomes have all been derived from pathogenic virus strains. An infectious cDNA copy of the well-characterized, non-pathogenic CVB3 strain GA genome was cloned in order to facilitate mapping of the CVB genes that influence expression of a virulence phenotype. Comparison of the sequence of the parental CVB3/GA population, derived by direct RT-PCR-mediated sequence analysis, to that of the infectious CVB3/GA progeny genome demonstrated that an authentic copy was cloned; numerous differences were observed in coding and non-coding sequences relative to other CVB3 strains. Progeny CVB3/GA replicated similarly to the parental strain in three different cell cultures and was avirulent when inoculated into mice, causing neither pancreatitis nor myocarditis. Inoculation of mice with CVB3/GA protected mice completely against myocarditis and pancreatitis induced by cardiovirulent CVB3 challenge. The secondary structure predicted for the CVB3/GA domain II, a region within the 5' non-translated region that is implicated as a key site affecting the expression of a cardiovirulent phenotype, differs from those predicted for cardiovirulent and pancreovirulent CVB3 strains. This is the first report characterizing a cloned CVB3 genome from an avirulent strain.
Lee
C-K
CK
Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
Kono
K
K
Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
Haas
E
E
Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
Kim
K-S
KS
Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
Drescher
K M
KM
Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
Chapman
N M
NM
Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
Tracy
S
S
Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center, 986495 Nebraska Medical Center, Omaha, NE 68198, USA.
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000517:prevention & control / Q000821:virology*; D016679:Genome, Viral; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000517:prevention & control / Q000821:virology; D010195:Pancreatitis / Q000517:prevention & control / Q000821:virology; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D014774:Virulence / Q000235:genetics
D020121:5' Untranslated Regions; D018076:DNA, Complementary; D012367:RNA, Viral