Twenty years of human bocavirus research: from an unculturable virus of unclear pathogenicity to a culturable human pathogen and gene therapy vector candidate

SUMMARYTwenty years after the first description of human bocavirus 1 (HBoV1) as a respiratory pathogen, significant progress has been made in both clinical and basic research; however, important clinical, diagnostic, and molecular challenges remain before bocavirus pathobiology is fully understood. The discovery of HBoV1 and its notorious prolonged shedding have challenged the new sensitive multiplex PCR panel-based diagnostic testing that replaced the old antigen assays, leading to erroneous classification of HBoV1 as an innocent bystander. Both sophisticated diagnostics and cytopathic effects in cell culture have now confirmed HBoV1 to be a common cause of upper and lower respiratory tract infections, mainly in children. While many questions have been answered, new questions have emerged as our understanding of parvoviruses has significantly expanded over the past two decades. In this review, key findings from 20 years of clinical, basic, and applied research on human bocaviruses are summarized and open questions highlighted to guide future investigations.