title: 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.affiliation: Department of Laboratory Medicine, University of California, San Francisco, 185 Berry Street, Box 0134, San Francisco, CA 94143-0134, USA. charles.chiu@ucsf.edu
authors.forename: C Y
authors.initials: CY
authors.lastname: Chiu
authors.forename: A L
authors.initials: AL
authors.lastname: Greninger
authors.forename: E C
authors.initials: EC
authors.lastname: Chen
authors.forename: T D
authors.initials: TD
authors.lastname: Haggerty
authors.forename: J
authors.initials: J
authors.lastname: Parsonnet
authors.forename: E
authors.initials: E
authors.lastname: Delwart
authors.forename: J L
authors.initials: JL
authors.lastname: Derisi
authors.forename: D
authors.initials: D
authors.lastname: Ganem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D017943:Cardiovirus / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification* / Q000502:physiology*; D018188:Cardiovirus Infections / Q000453:epidemiology* / Q000821:virology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D003967:Diarrhea / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D016036:Seroepidemiologic Studies; D014481:United States / Q000453:epidemiology; D014779:Virus Replication; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012367:RNA, Viral