Characterization of an infectious cDNA copy of the genome of a naturally occurring, avirulent coxsackievirus B3 clinical isolate

J Gen Virol. 2005 Jan;86(Pt 1):197-210. doi: 10.1099/vir.0.80424-0.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Disease Models, Animal
  • Enterovirus B, Human / genetics*
  • Enterovirus B, Human / immunology
  • Enterovirus B, Human / pathogenicity
  • Enterovirus Infections / prevention & control
  • Enterovirus Infections / virology*
  • Genome, Viral*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Myocarditis / prevention & control
  • Myocarditis / virology
  • Pancreatitis / prevention & control
  • Pancreatitis / virology
  • Phenotype
  • RNA, Viral / genetics
  • Sequence Alignment
  • Virulence / genetics

Substances

  • 5' Untranslated Regions
  • DNA, Complementary
  • RNA, Viral

Associated data

  • GENBANK/AY673831