Name
The reovirus S4 gene that encodes σ3 is a critical determinant of myocarditis in neonatal mice
Presenter
Meleana Hinchman, Cornell University
Co-Author(s)
Meleana Hinchman, Cornell University
Yingying Guo, Tianjin Medical University, Tianjin, 300070, China.
Kevin Milza, Cornell University
Dylan Beegal, Cornell University
Andrew Miller, Cornell University
John S. L. Parker, Cornell University
Abstract Category
Pathogenesis and Immunity
Abstract
Viral infection is a leading cause of myocarditis. The resulting damage can cause heart failure or sudden death, particularly in children and young adults, and reliable methods to diagnose it are still lacking.
Oral infection of neonatal mice with some reovirus (REOV) strains causes myocarditis. The serotype 1 Lang (T1L) is non-lethal and mildly myocarditic in 30-50% of inoculated neonatal mice. In contrast, a reassortant virus containing serotype 3 Dearing (T3D) M2 gene in the T1L background causes severe myocarditis and up to 90% lethality in survival studies. In previous work, we showed that a point mutant (K287T) of σ3 encoded by the REOV S4 gene abolished the myocarditic capacity of T1L.
Here, we evaluated the effect of introducing σ3 point mutations on virulence and replicative capacity of the T1L-T3DM2 reassortant. We find that the K287T mutation in σ3 negates the virulence of the T1L-T3DM2 reassortant and alters its replicative capacity. All mice challenged with the reassortant containing the K287T mutation survived and had normal-appearing hearts at the end of the experiment. The level of viral antigen detected by immunofluorescence in the hearts of mice infected with T1L-S4(K287T)/T3DM2 was substantially reduced compared to T1L/T3DM2. Histological scoring of the hearts of infected mice revealed significantly lower levels of inflammation in those infected with the mutant compared to the parental reassortant. These results indicate that σ3 is a critical determinant of virus-induced heart disease in the neonatal mouse REOV model.
Oral infection of neonatal mice with some reovirus (REOV) strains causes myocarditis. The serotype 1 Lang (T1L) is non-lethal and mildly myocarditic in 30-50% of inoculated neonatal mice. In contrast, a reassortant virus containing serotype 3 Dearing (T3D) M2 gene in the T1L background causes severe myocarditis and up to 90% lethality in survival studies. In previous work, we showed that a point mutant (K287T) of σ3 encoded by the REOV S4 gene abolished the myocarditic capacity of T1L.
Here, we evaluated the effect of introducing σ3 point mutations on virulence and replicative capacity of the T1L-T3DM2 reassortant. We find that the K287T mutation in σ3 negates the virulence of the T1L-T3DM2 reassortant and alters its replicative capacity. All mice challenged with the reassortant containing the K287T mutation survived and had normal-appearing hearts at the end of the experiment. The level of viral antigen detected by immunofluorescence in the hearts of mice infected with T1L-S4(K287T)/T3DM2 was substantially reduced compared to T1L/T3DM2. Histological scoring of the hearts of infected mice revealed significantly lower levels of inflammation in those infected with the mutant compared to the parental reassortant. These results indicate that σ3 is a critical determinant of virus-induced heart disease in the neonatal mouse REOV model.