title: B-Cell Responses to Human Bocaviruses 1-4: New Insights from a Childhood Follow-Up Study.
abstract: Human bocaviruses (HBoVs) 1-4 are recently discovered, antigenically similar parvoviruses. We examined the hypothesis that the antigenic similarity of these viruses could give rise to clinically and diagnostically important immunological interactions. IgG and IgM EIAs as well as qPCR were used to study ~2000 sera collected from infancy to early adolescence at 3-6-month intervals from 109 children whose symptoms were recorded. We found that HBoV1-4-specific seroprevalences at age 6 years were 80%, 48%, 10%, and 0%, respectively. HBoV1 infections resulted in significantly weaker IgG responses among children who had pre-existing HBoV2 IgG, and vice versa. Furthermore, we documented a complete absence of virus type-specific immune responses in six viremic children who had pre-existing IgG for another bocavirus, indicating that not all HBoV infections can be diagnosed serologically. Our results strongly indicate that interactions between consecutive HBoV infections affect HBoV immunity via a phenomenon called "original antigenic sin", cross-protection, or both; however, without evident clinical consequences but with important ramifications for the serodiagnosis of HBoV infections. Serological data is likely to underestimate human exposure to these viruses.
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland.
authors.forename: Kalle
authors.initials: K
authors.lastname: Kantola
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland; Helsinki University Hospital Laboratory Services, Helsinki, Finland.
authors.forename: Lea
authors.initials: L
authors.lastname: Hedman
authors.affiliation: Turku University Hospital, Department of Pediatrics, Turku, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Tanner
authors.affiliation: Medicity, University of Turku, Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Simell
authors.affiliation: Medicity, University of Turku, Turku, Finland.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Mäkinen
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland.
authors.forename: Juulia
authors.initials: J
authors.lastname: Partanen
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: University of Oulu, Department of Pediatrics, Oulu, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Veijola
authors.affiliation: University of Helsinki and Helsinki University Hospital, Children's Hospital and Research Programs Unit, Diabetes and Obesity, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Tampere University Hospital, Tampere Center for Child Health Research, Tampere, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Turku University Hospital, Department of Pediatrics, Turku, Finland; Medicity, University of Turku, Turku, Finland; University of Eastern Finland, Department of Clinical Microbiology, Kuopio, Finland; University of Turku, Immunogenetics Laboratory, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.affiliation: University of Tampere, Department of Virology, Tampere, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Hyöty
authors.affiliation: Turku University Hospital, Department of Pediatrics, Turku, Finland; Medicity, University of Turku, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Medicity, University of Turku, Turku, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland; Helsinki University Hospital Laboratory Services, Helsinki, Finland.
authors.forename: Klaus
authors.initials: K
authors.lastname: Hedman
authors.affiliation: University of Helsinki, Department of Virology, Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Söderlund-Venermo
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056661:Human bocavirus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007223:Infant; D008297:Male; D010322:Parvoviridae Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction; D016036:Seroepidemiologic Studies; D012698:Serologic Tests; D014766:Viremia / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M