Seroepidemiology of Human Bocaviruses 1–4

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Abstract
Background. Recently, 3 new members of the genus Bocavirus, human bocavirus 2 (HBoV2), human bocavirus 3 (HBoV3), and human bocavirus 4 (HBoV4), were discovered. HBoV2–4 occur mainly in the gastrointestinal tract but rarely in the respiratory tract, contrary to human bocavirus 1 (HBoV1). Methods. To investigate HBoV1–4 seroepidemiology among 195 adults and 252 wheezing children, we conducted immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme immunoassays with recombinant viruslike particles (VLPs). The children’s sera were also tested for HBoV1–4 DNA by quantitative polymerase chain reaction (qPCR). Results. Both rabbit and human antibodies to HBoV1–4 VP2 VLPs were found to be cross-reactive. After depletion of HBoV1-reactive antibodies, the HBoV2–4 approximate seroprevalences in adults were 34%, 15%, and 2% and in children aged 1–2 years 25%, 10%, and 5%, respectively. After depletion of HBoV2–4-reactive antibodies, the HBoV1 seroprevalence among adults decreased from 96% to 59%. No cross-reactivity of human anti-HBoV IgG was observed with bovine parvovirus1, parvovirus B19 or PARV4. No child was HBoV2–4 viremic. Conclusions. HBoV2–4 infect humans less commonly and elicit weaker B-cell responses than HBoV1. In our study HBoV2–4 did not seem to have a major etiological role in wheezing. Cross-reactivity with HBoV2–4 IgG partially accounts for the high HBoV1 seroprevalences previously reported. Correction for cross-reactivity is a prerequisite for VLP-based HBoV seroepidemiology.