Cultivation and serological characterization of a human Theiler's-like cardiovirus associated with diarrheal disease.

Abstract

Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.

• Authors: C Y Chiu, A L Greninger, E C Chen, T D Haggerty, J Parsonnet, E Delwart, J L Derisi, D Ganem
• Journal: Journal of virology (J Virol) Vol. 84 Issue 9 Pg. 4407-14 (May 2010) ISSN: 1098-5514 [Electronic] United States
• PMID: 20164225 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• RNA, Viral

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• Cardiovirus (genetics, growth & development, isolation & purification, physiology)
• Cardiovirus Infections (epidemiology, virology)
• Cell Line
• Cytopathogenic Effect, Viral
• Diarrhea (virology)
• Feces (virology)
• Female
• Genotype
• Humans
• Male
• Middle Aged
• Molecular Sequence Data
• RNA, Viral (genetics)
• Sequence Analysis, DNA
• Seroepidemiologic Studies
• United States (epidemiology)
• Virus Replication
• Young Adult