Human Bocavirus (HBoV):
Genus Bocaparvovirus, Family (Parvoviridae), Class II, (linear) ssDNA genome, non-enveloped, icosahedral virion
Scientific article that first reported on the new virus:
Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(36):12891-12896. doi:10.1073/pnas.0504666102.
News article:
There has not really been a first report on human bocavirus in the news, as it is something wasn’t discovered through a widely publicized epidemic. However, it has been recently mentioned as a part of a new delivery system for gene therapy for cystic fibrosis. It has also been mentioned in an article from 2016 to have antigen tests developed for it.
Interest:
This virus first jumped out at me when I saw its relation to respiratory illness. I have struggled with respiratory issues all my life, with chronic asthma, and various infections. At the time of assignment, I had a case of walking pneumonia and the prevalence of the virus in cases of respiratory illness was particularly interesting.
Discovery:
The scientists at the Karolinska Institute used a novel technique to identify the new species. Samples of nasopharyngeal aspirates were centrifuged to be cell-free (Allander et al., 2005). The supernatants were then ultracentrifuged for virus concentration, then depleted of nonviral nucleic acid by filtration and treatment with DNase. Products were then amplified with random PCR, cloned, and then sequenced . They were then put through database searches for the sequencing results. 20% of the final clones showed similarity to viral sequences, and matched 7 different viral species. Parvovirus-like sequences were found and showed no significant similarity to database sequences at the nucleotide level, but significantly matched those of bovine parvovirus (BPV) and canine minute virus (MVC) at an amino acid level.
Prevalence:
Based on sequencing analysis, HBoV likely evolved through zoonosis and entered the human population between 60 and 300 years ago. Due to its presence in other carnivore hosts and similarity to the sequences of BPV and MVC, it is likely that a dog or cow bit a human or vice versa (Babkin et al., 2013). Human bocavirus is limited to humans, and can be found in nasopharyngeal, serum, fecal and urine samples. Because of its very high copy numbers in respiratory tract secretions, aerosol and contact transmission are likely effective, as they are for other respiratory viruses (Schildgen et al., 2008) The worldwide presence of HBoV in respiratory tract infections has been confirmed by numerous studies and was detected in 1% to 57% of all samples. Furthermore, the worldwide HBoV total prevalence estimates in respiratory infections is 6.3% and in gastrointestinal infections is 5.9%. HBoV infection is typically more prevalent in children than adults. The seroprevalence of HBoV is age-related and goes from 40% in children between 18 and 23 mo of age up to almost 100% in children older than 2, and averaged 76.6% in children and 96% in adults. (Guido et al., 2016). Four different subtypes have been identified, and are found worldwide without any regional or geographic restrictions (Schildgen and Schildgen 2012). However, many of these studies have found an unusually high number of coinfections where HBoV occurs simultaneously with other viruses. It is thus hard to determine the association of HBoV with disease.
Virology:
The HBoV virion is a non-enveloped icosahedra capsid, T=1. The virus capsid proteins bind to unknown cell receptors and initiate clathrin-mediated endocytosis of the virion into the host cell. It then penetrates the cytoplasm via permeabilization of the host endosomal membrane and is transported to the nucleus. HBoV is a parvovirus, which is among the smallest of all viruses and as such the virus capsid is small enough to cross the nuclear pore complex. It then uncoats inside the nucleus This small size makes the virus more dependent on the host cell, and as such cannot induce cells to enter DNA synthesis and can only productively infect cells going through S phase. HBoV and other parvoviruses have very few genes. Unlike the genomes of ssDNA bacteriophages, parvoviruses have linear genomes whose ends can anneal to form hairpin structures. The hairpin structures can enable DNA replication by serving as primers for DNA polymerase. The current model for replication indicates that parvoviruses replicate their DNA in a ‘rolling-hairpin’ model (Schildgen et al., 2012). With some DNA gymnastics, terminal hairpins are unwound and copied by to create an extended DNA strand and then reformed to prime synthesis of the other side of the hairpin. The newly formed dsDNA molecule has a hairpin end and results in displacement of progeny ssDNA. This allows the virus to copy its genome with rolling circle replication but solve the problem of end replication. There are three ORFs which are transcribed by RNA polymerase II and can be spliced to generate six different mRNAs. More work needs to be done to describe virion assembly and release, but the mechanism is likely similar to that of MVC or BPV.
Infection of the host:
HBoV infection is clinically indistinguishable from the “common cold.” The infection is hypothesized to start in the upper airways and by swallowing and can enter the bloodstream via the lungs or gastrointestinal tract. It can then lead to diarrhea, bronchitis, and other inflammation. Rarely, HBoV has also been associated with encephalitis. As mentioned before, its high copy number and presence in multiple bodily fluids makes aerosol and contact transmission effective. HBoV has been identified in 20% of colorectal and lung tumors, which suggests that HBoV may be associated with chronic disease.
However, HBoV has been co-detected with other pathogens in respiratory illness at a high rate. One hypothesis suggests that HBoV may be a bystander, instead of a pathogen. Recently, mounting evidence has indicated its role as one of the major causes of acute respiratory illness and wheezing in children. It has been shown that the virus causes mild to severe tissue damage in cell culture, which is typical of a pathogenic virus (Deng et al., 2013). There is currently no approved treatment for HBoV infection, and so treatment is usually limited to that of symptoms. There has only been one published case of antiviral treatment of HBoV where a boy who suffered from an immunodeficiency was treated with cidovere. The HBoV infection was successfully eliminated in that case.
Interesting things that came up during preparation of this report:
I found it fascinating that molecular screening techniques were used to find a virus that is so prevalent that was hitherto unidentified. The fact that they were able to discover a new infectious disease with these methods provides a new way to detect unknown samples in batches of samples that is independent of cell-culture techniques.
The sheer range and prevalence of the virus is also interesting. HBoV is distributed all over the world at high rates in acute respiratory infection as well as chronic illness. It is also interesting to note the effect that the virus has on the gastrointestinal tract. This virus can contribute to gastroenteritis, and may even be an etiological agent. Unfortunately, parvovirus is very hardy and can be hard to treat in these cases as well. The presence of HBoV in a large number of bodily fluids is disturbing and means that the virus has more opportunities and vectors by which to spread. Nasal secretions could be swallowed, and fecal oral transmission could occur as well. It will be very interesting to see the research on HBoV develop in the coming years.