Exploring evidence from cells to clinics: is human bocavirus a gastrointestinal pathogen or just a risk factor?

Human bocaviruses (HBoVs), first identified in 2005 and composed of genotypes 1–4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. HBoV-1 has been primarily associated with respiratory symptoms, while HBoV2-4 are mostly found in gastrointestinal (GI) samples. Results from case-control studies are still controversial; however, epidemiological evidence has shown a significant association between HBoV-2 and gastroenteritis. This review will primarily focus on this association, with a brief discussion of evidence related to other HBoV genotypes. Pathological and molecular studies on the pathogenesis of HBoV, particularly in GI cells, are very scarce, possibly due to the difficulties of in vitro HBoV culture. Nonetheless, some relevant findings from colorectal cancer samples have yielded valuable insights regarding the behavior of HBoV in the GI system. In the present review, we provide an updated overview of the epidemiological evidence for an association of HBoV infection with acute gastroenteritis and focus on the cellular and molecular perspectives of HBoV pathogenicity. Finally, we look at the knowledge gaps about how HBoV affects the GI system and explore future directions.