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Published on: June 9, 2011
Cultivation and serological characterization of a human Theiler's-like cardiovirus associated with diarrheal disease
C Y Chiu1, A L Greninger, E C Chen
1Department of Laboratory Medicine, University of California, San Francisco, 185 Berry Street, Box 0134, San Francisco, CA 94143-0134, USA. charles.chiu@ucsf.edu
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.
Insights
Researchers isolated and characterized a common human cardiovirus (genotype 2). This work advances understanding of cardiovirus infection, which is widespread and linked to diarrheal disease.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Cardioviruses, including Theiler's murine encephalomyelitis virus (TMEV), are picornaviruses known to cause disease in rodents.
- Human cardioviruses, such as Saffold virus (SAFV) and human TMEV-like cardiovirus (HTCV), have been identified, with genotype 2 strains being most prevalent.
- Previous difficulties in in vitro propagation of genotype 1 and 2 cardioviruses have limited research into their prevalence and pathogenicity.
Purpose of the Study:
- To isolate and characterize a genotype 2 human cardiovirus (HTCV-UC6).
- To investigate methods for successful in vitro cultivation of difficult-to-propagate cardioviruses.
- To assess the seroprevalence of genotype 2 cardioviruses in the human population and explore potential clinical associations.
Main Methods:
- Isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6) from stool samples.
- Utilized cytokine-blocking antibodies to facilitate viral cultivation by interrupting antiviral pathways.
- Conducted serologic assays to determine antibody prevalence and neutralizing antibody responses in U.S. adults.
- Documented a case of acute cardiovirus seroconversion in a child presenting with gastrointestinal symptoms.
Main Results:
- Successfully isolated and cultivated the genotype 2 human cardiovirus HTCV-UC6, requiring cytokine-blocking antibodies for propagation.
- HTCV-UC6 exhibited slower replication kinetics and a moderate cytopathic effect compared to other cardioviruses.
- Serologic data indicated high seroprevalence (91%) of genotype 2 cardioviruses in U.S. adults, with 80% having neutralizing antibodies.
- Observed and reported the first evidence of cardiovirus infection associated with diarrheal disease in a child.
Conclusions:
- The successful cultivation of HTCV-UC6 provides a valuable tool for studying genotype 2 human cardioviruses.
- Widespread human cardiovirus infection is confirmed, with a high prevalence of neutralizing antibodies against genotype 2 strains.
- This study presents the first direct evidence linking human cardiovirus infection to diarrheal illness, opening new avenues for research.
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