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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.

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Background: Prediction tools that combine polygenic risk scores with clinical factors provide a new opportunity for improved prediction and prevention of atherosclerotic cardiovascular disease, but the clinical utility of polygenic risk score has remained unclear. Methods: We collected a prospective cohort of 7342 individuals (64% women, mean age 56 years) and estimated their 10-year risk for atherosclerotic cardiovascular disease both by a traditional risk score and a composite score combining the effect of a polygenic risk score and clinical risk factors. We then tested how returning the personal risk information with an interactive web-tool impacted on the participants’ health behavior. Results: When reassessed after 1.5 years by a clinical visit and questionnaires, 20.8% of individuals at high (>10%) 10-year atherosclerotic cardiovascular disease risk had seen a doctor, 12.4% reported weight loss, 14.2% of smokers had quit smoking, and 15.4% had signed up for health coaching online. Altogether, 42.6% of persons at high risk had made one or more health behavioral changes versus 33.5% of persons at low/average risk such that higher baseline risk predicted a favorable change (OR [CI], 1.53 [1.37–1.72] for persons at high risk versus the rest, P <0.001), with both high clinical ( P <0.001) and genomic risk (OR [CI], 1.10 [1.03–1.17], P =0.003) contributing independently. Conclusions: Web-based communication of personal atherosclerotic cardiovascular disease risk-data including polygenic risk to middle-aged persons motivates positive changes in health behavior and the propensity to seek care. It supports integration of genomic information into clinical risk calculators as a feasible approach to enhance disease prevention.

We developed a multiplex, solid-phase minisequencing method to detect multiple single-nucleotide polymorphisms in an undivided sample. The amplified DNA templates are first captured on a manifold. Then, with multiple minisequencing primers of various sizes, single-nucleotide extension reactions are carried out simultaneously with fluorescently labeled dideoxynucleotides. The size of the extended product, determined by using a DNA sequencing instrument, defines the site of the polymorphisms, and the incorporated nucleotide gives the identity of the nucleotide at each site. HLA-DQA1 typing was used as a model system to evaluate the method. The DR2 subgroup of the HLA-DRB1 gene was typed along with the DQA1 gene to demonstrate the feasibility of the method in analyzing multiple genes at multiple sites simultaneously. The method is generally applicable for screening any single-nucleotide polymorphisms or point mutations, and its manifold format allows practical handling of large numbers of samples.

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