Human bocavirus (HBoV) is the name given to all viruses in the genus Bocaparvovirus of virus family Parvoviridae that are known to infect humans. HBoV1 and HBoV3 (and gorilla bocaparvovirus) are members of species Primate bocaparvovirus 1 whereas viruses HBoV2 and HBoV4 belong to species Primate bocaparvovirus 2. Some of these viruses cause human disease. HBoV1 is strongly implicated in causing some cases of lower respiratory tract infection, especially in young children, and several of the viruses have been linked to gastroenteritis, although the full clinical role of this emerging infectious disease remains to be elucidated.
History Allander and colleagues at the Karolinska Institutet in Stockholm, Sweden, first cloned the coding sequence of this new member of the family of Parvoviridae in 2005 from pooled nasopharyngeal aspirates (NPA, collection of aspirated fluid from the back of the nasal cavity). They used a novel technique called molecular virus screening, based on random cloning and bioinformatical analysis. This technique has led to the discovery of new viruses such as polyomavirus KI (Karolinska Institute) and WU (Washington University), which are closely related to each other and have been isolated from respiratory secretions. Several groups of scientists have since then found that HBoV is the fourth most common virus in respiratory samples, behind rhinoviruses, respiratory syncytial virus, and adenoviruses. The name bocavirus is derived from bovine and canine, referring to the two known hosts for the founder members of this genus; bovine parvovirus which infects cattle, and minute virus of canines which infects dogs. Parvoviruses (Latin: small viruses) have a 5 kilobase long single-stranded DNA, and they use some of their host's replication proteins to copy their DNA.
Virology The virions are small (diameter 18–26 nanometers), icosahedral and non enveloped. The capsid has T = 1 symmetry and consists of 60 copies of coat protein. The coat proteins have a conserved, eight stranded beta barrel motif that forms the core of the capsid. There is also a conserved alpha helix. The HBoV capsid shares three characteristic features also found in the other vertebrate parvoviruses: (1) a dimple like depression at each icosahedral 2-fold axis; (2) a large trimeric protrusion at or surrounding each 3-fold axis; (3) a cylindrical projection surrounding each 5-fold axis that encloses a central channel which connects the inside of the particle with its exterior and serves as the entry and exit portal for viral DNA. This 5-fold cylinder is itself encircled by a wide canyon like depression. While the dimple is also found among the invertebrate parvoviruses, they typically lack the 3-fold protrusions and canyon around the 5-fold channel. The external diameter of the capsid ranges from ~21.5 nanometers (nm) at the lowest points of the dimple and canyon to ~28 nm at the top of the protrusion. The genome is a linear, single-stranded DNA 5.5 kilobases in length with disparate terminal hairpin structures at each end. The genome encodes 3 open reading frames (ORF1, 2 and 3). The left ORF encodes 4 non structural proteins (NS1, NS2, NS3 and NS4). The middle ORF encodes NP1. The right hand ORF (ORF3) encodes the capsid proteins (VP1, VP2, and VP3). The NP1 gene is in an alternate reading frame to VP1 and overlaps the start of VP1 by 13 nucleotides. Similarly, VP3 is collinear to VP1 and VP2 and results from initiation of translation at a downstream ATG and co-terminates. VP2 is translated from a non-canonical start codon GUG. A viral noncoding RNA of 140 nucleotides, named as bocavirus-encoded small RNA (BocaSR), is expressed from the 3' noncoding region after the VP ORF. NP1 is a small non-structural protein that could induce apoptosis in transfection of HeLa cells. There is a single promoter located within the 3' hairpin. This is responsible for, by alternative splicing and alternative polyadenylation, for the generation of several (at least 6) mRNAs. The poly A tail is about 150 nucleotides in length. After nuclear import the single stranded genome is converted to double stranded DNA and production of the viral NS1 protein commences. The genome is replicated through a unique linear rolling hairpin mechanism that is dependent on the NS1 protein. Replication has been reported to result in the creation of a series of circular head to tail sequences. A sequence conserved among the Parvoviridae TAAAAAT is found close to the 3' terminus. Other parvoviruses replicate only when the host cell is in S phase: viral replication results in the death of the host cell. This pattern has not yet been experimentally confirmed for the bocaviruses but seems likely to be the case. Expression of the viral proteins alone does not cause host cell death unlike other parvoviruses where this has been examined.
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