Properties of coxsackievirus B3 variants which are amyocarditic or myocarditic for mice

Abstract

Inoculation of adolescent CD-1 mice with one variant of coxsackievirus B3 (CVB3m) results in induction of readily observable myocardial lesions, whereas inoculation of siblings with a second variant (CVB3o) results in little or no myocarditis. These variants could not be distinquished from each other on the basis of replication properties in HeLa cells or cardiac tissues in vivo, sensitivity to human interferon in HeLa cells, induction of interferon in the mouse, generation of detectable levels of defective-interfering particles in HeLa cells or in cardiac tissue in vivo, stimulation of serum-neutralizing antibody titers, nor in their rate of clearance by the spleen. Infectivity of CVB3o was slightly more heat labile at 34 degrees C than CVB3m. Little if any replication of either CVB3o or CVB3m occurred in either adherent or nonadherent populations of normal murine lymphoid cells. Cardiac tissues from mice inoculated with CVB3m but not CVBo contain new antigens that can inhibit migration of sensitized lymphocytes from CVB3m-immunized mice in an in vitro cell-migration-inhibition assay. However, the CVB3o variant was shown to have the genetic capability of inducing myocarditis if the mice were treated with cyclophosphamide prior to virus inoculation. These results suggest, in agreement with our previously published work, that induction of myocarditis by CVB3 requires destruction of myocytes by virus and subsequent stimulation of cell-mediated responses to new antigens produced in the myocardium during virus replication.

Toward Testing the Hypothesis that Group B Coxsackieviruses (CVB) Trigger Insulin-Dependent Diabetes: Inoculating Nonobese Diabetic Mice with CVB Markedly Lowers Diabetes Incidence

“…6E). In no instance did we detect myocarditis (data not shown), classically observed in many inbred strains of mice inoculated with virulent strains such as these (36,103). Greater extents of protection from T1D by pathogenic CVB3 strains were regularly associated with CVB3-induced pancreatitis.…”

“…To characterize this system in greater detail, we selected two strains of CVB3 for further analysis. The pathogenic strain CVB3/M (which is capable of inducing both pancreatitis and myocarditis in inbred mice [19,36,105]) and the avirulent strain CVB3/GA (which replicates well in mice but induces no apparent disease [105]) represent polar ends of the established CVB pathogenicity spectrum (105).…”

Coxsackievirus B1-induced murine myositis: no evidence for viral persistence

“…Several animal models have been developed, in which pancreatitis (Vella et al, 1992), cardiomyopathy (Gauntt et al, 1979) and myositis (Ray et al, 1979) are induced by infection with specific strains of coxsackie B viruses. Ray et al (1979) described a murine model for myositis induced by a coxsackievirus B1 infection of suckling mice.…”

Expression of an Antigenic Adenovirus Epitope in a Group B Coxsackievirus

“…The cells were grown at 37°C in a humidified 5% CO 2 -air mixture. The infectious cDNA copy of the CVB3/0 genome (15,16,28) (GenBank accession no. M88483) was used as the background for the construction of the Ad2 hexon L1 loop polypeptide-expressing chimeric strain, CVB3-PL2-Ad2L1.…”