Human bocavirus: Current knowledge and future challenges

Abstract

Human bocavirus (HBoV) is a parvovirus isolated about a decade ago and found worldwide in both respiratory samples, mainly from early life and children of 6-24 mo of age with acute respiratory infection, and in stool samples, from patients with gastroenteritis. Since then, other viruses related to the first HBoV isolate (HBoV1), namely HBoV2, HBoV3 and HBoV4, have been detected principally in human faeces. HBoVs are small non-enveloped single-stranded DNA viruses of about 5300 nucleotides, consisting of three open reading frames encoding the first two the non-structural protein 1 (NS1) and nuclear phosphoprotein (NP1) and the third the viral capsid proteins 1 and 2 (VP1 and VP2). HBoV pathogenicity remains to be fully clarified mainly due to the lack of animal models for the difficulties in replicating the virus in in vitro cell cultures, and the fact that HBoV infection is frequently accompanied by at least another viral and/or bacterial respiratory and/or gastroenteric pathogen infection. Current diagnostic methods to support HBoV detection include polymerase chain reaction, real-time PCR, enzyme-linked immunosorbent assay and enzyme immunoassay using recombinant VP2 or virus-like particle capsid proteins, although sequence-independent amplification techniques combined with next-generation sequencing platforms promise rapid and simultaneous detection of the pathogens in the future. This review presents the current knowledge on HBoV genotypes with emphasis on taxonomy, phylogenetic relationship and genomic analysis, biology, epidemiology, pathogenesis and diagnostic methods. The emerging discussion on HBoVs as true pathogen or innocent bystander is also emphasized.

Keywords: Epidemiology; Gastrointestinal virus; Human bocavirus; Immunoassay methods; Molecular tests; Pathogenesis; Respiratory virus.

Figure 1

Genomic organization of Human Bocaviruses. Schematic maps of the Human Bocavirus genomes (HBoV1, RefSeq. NC_007455.1; HBoV2, RefSeq. NC_012042.1; HBoV3, RefSeq. NC_012564.1; HBoV4, RefSeq. NC_012729.2) were obtained using the Illustrator of Biological Sequences software package[55]. The genes encoding the protein NS1 (non-structural protein), NP1 and VP1/VP2 (capsid proteins) and their nucleotide positions are shown.

Figure 2

Similarity plot (generated by SimPlot)[56] of Human Bocaviruses genomes. Each curve is a comparison between the HBoV1 genome (reference) and HBoV2-4 sequences. Nucleotide sequences were aligned using Clustal Omega[57] and the plot was rendered by Simplot using a window size of 200 bp and a step size of 20 bp. The horizontal bars above the curves represent the HBoV1 genes arranged as indicated in Figure 1; Phylogenetic trees of nucleotide and amino acid sequences of the HBoV genes. Sequences were aligned by Clustal Omega and phylogenetic analysis was carried out using the Neighbor-Joining method implemented in the MEGA5 program[58]. The numbers at the branch nodes indicate the bootstrap values calculated with 1000 replicates.