MicrobiologyBytes

Parvoviruses are small non-enveloped, icosahedral DNA viruses with a diameter of 18–26 nm that encapsidate a single-stranded genome of approximately (~)5–6 kb. To date, there are a number of parvoviruses known to infect humans, including adeno-associated viruses (AAVs), parvovirus B19 (B19V), and two newly identified human parvoviruses, which are the human bocavirus (HBoV) and human parvovirus 4 (PARV4).

HBoV was firstly identified in respiratory samples from children with lower respiratory tract infections and subsequently proven epidemiologically to be associated with the diseases. PARV4 was initially found in a blood sample from an intravenous drug user with acute viral infection syndrome. Subsequently, the PARV4 genome was detected in human plasma pools at a low titer. PARV4 had also been found in the livers of hepatitis C virus-positive individuals and the bone marrow of HIV-positive individuals. Recently, PARV4 DNA was detected in cerebrospinal fluid of two children with encephalitis of unknown etiology – however, the disease association of PARV4 remains unclear.

HBoV has been classified as a member in the genus Bocavirus based on the similarity of its genome sequence with those of the two animal bocaviruses. However, the known PARV4 incomplete genome, which lacks information of the terminal repeats, does not show a close relationship to any of the known parvoviruses in the genera of the family Parvoviridae that have been classified to date. This has led to the proposed classification of the PARV4 and PARV4-like viruses as members in a new genus called Partetravirus in the family Parvoviridae by the International Committee on Taxonomy of Viruses (ICTV).

Little is known about the gene expression of PARV4 and the function of PARV4 proteins. Since the PARV4 has not been cultured in vitro, and the full-length genome with terminal repeats has not been sequenced, researchers profiled the gene expression of PARV4 by transfecting a replication-competent PARV4 genome. This study has revelealed for the first time the detailed transcription map of PARV4, which can be beneficial for subsequent study of PARV4 infection.

Molecular characterization of the newly identified human parvovirus 4 in the family Parvoviridae. Virology. Oct 30 2011
Human parvovirus 4 (PARV4) is an emerging human virus, and little is known about the molecular aspects of PARV4 apart from its incomplete genome sequence, which lacks information of the termini. We analyzed the gene expression profile of PARV4 using a nearly full-length HPV4 genome in a replication competent system in 293 cells. We found that PARV4 utilizes two promoters to transcribe non-structural protein- and structural protein-encoding mRNAs, respectively, which were polyadenylated at the right end of the genome. Three major proteins, including the large non-structural protein NS1a, whose mRNA is spliced, and capsid proteins VP1 and VP2, were detected. Additional functional analysis of the NS1a revealed its capability to induce cell cycle arrest at G2/M phase in ex vivo-generated human hematopoietic stem cells. Taken together, our characterization of the molecular features of PARV4 suggests that PARV4 represents a new genus in the family Parvoviridae.

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Human bocavirus (HBoV) was discovered in 2005. HBoV has been detected in patients suffering from respiratory infections and gastrointestinal diseases, but a proof that HBoV is the causative agent in such cases is missing as it remains impossible so far to fulfil Koch’s modified postulates. The latter problem is caused by the fact that HBoV is difficult to propagate in cell culture and that no animal model is available.

Since HBoV infections are accompanied by co-pathogens in a very high frequency, it has been suggested that HBoV is a passenger rather than a pathogen in airway infections, despite the fact that HBoV causes a productive infection with viral shedding, viremia, and putative persistence in different organs. Although HBoV meanwhile was classified as an autonomous parvovirus rather than a Dependovirus like the Adeno-associated virus (AAV), there remains the possibility that HBoV infections depend on helper viruses or at least contributes synergistically to the clinical course of disease.

Does human bocavirus infection depend on helper viruses? A challenging case report. Virology Journal 2011, 8: 417 doi:10.1186/1743-422X-8-417
A case of severe diarrhoea associated with synergistic human bocavirus type 1 (HBoV) and human herpes virus type 6 (HHV6) is reported. The case supports the hypotheses that HBoV infection under clinical conditions may depend on helper viruses, or that HBoV replicates by a mechanism that is atypical for parvoviruses, or that HBoV infection can be specifically treated with cidofovir.

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Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. However, in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, researchers screened fecal samples from symptomatic children using a molecular degenerate amplification technique and detected the presence of a novel parvovirus, Human Bocavirus species 2 (HBoV2). The genome of HBoV2 is 23% variant from its closest relative, the human bocavirus, a member of the Bocavirus genus of the Parvovirinae. Using specific amplification assays, they found HBoV2 was the third most prevalent virus detected in samples from symptomatic children in a case control study of AGE. Further, they found virus presence was associated with symptoms. During this screening, they detected a second related parvovirus, now named Human Bocavirus species 3 (HBoV3), but the prevalence was low and not associated with symptoms. The discovery of HBoV2 has reduced the diagnostic gap, but more studies are required to further investigate its role in AGE.

A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children. 2009 PLoS Pathog 5(4): e1000391
Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemar’s Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study.

Related:

• Newly discovered respiratory viruses