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Journal of Virology Jun 2017Bocaparvoviruses are emerging pathogens of the family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal...
Bocaparvoviruses are emerging pathogens of the family. Human bocavirus 1 (HBoV1) causes severe respiratory infections and HBoV2 to HBoV4 cause gastrointestinal infections in young children. Recent reports of life-threatening cases, lack of direct treatment or vaccination, and a limited understanding of their disease mechanisms highlight the need to study these pathogens on a molecular and structural level for the development of therapeutics. Toward this end, the capsid structures of HBoV1, HBoV3, and HBoV4 were determined to a resolution of 2.8 to 3.0 Å by cryo-electron microscopy and three-dimensional image reconstruction. The bocaparvovirus capsids, which display different tissue tropisms, have features in common with other parvoviruses, such as depressions at the icosahedral 2-fold symmetry axis and surrounding the 5-fold symmetry axis, protrusions surrounding the 3-fold symmetry axis, and a channel at the 5-fold symmetry axis. However, unlike other parvoviruses, densities extending the 5-fold channel into the capsid interior are conserved among the bocaparvoviruses and are suggestive of a genus-specific function. Additionally, their major viral protein 3 contains loops with variable regions at their apexes conferring capsid surface topologies different from those of other parvoviruses. Structural comparisons at the strain (HBoV) and genus (bovine parvovirus and HBoV) levels identified differences in surface loops that are functionally important in host/tissue tropism, pathogenicity, and antigenicity in other parvoviruses and likely play similar roles in these viruses. This study thus provides a structural framework to characterize determinants of host/tissue tropism, pathogenicity, and antigenicity for the development of antiviral strategies to control human bocavirus infections. Human bocaviruses are one of only a few members of the family pathogenic to humans, especially young children and immunocompromised adults. There are currently no treatments or vaccines for these viruses or the related enteric bocaviruses. This study obtained the first high-resolution structures of three human bocaparvoviruses determined by cryo-reconstruction. HBoV1 infects the respiratory tract, and HBoV3 and HBoV4 infect the gastrointestinal tract, tissues that are likely targeted by the capsid. Comparison of these viruses provides information on conserved bocaparvovirus-specific features and variable regions resulting in unique surface topologies that can serve as guides to characterize HBoV determinants of tissue tropism and antigenicity in future experiments. Based on the comparison to other existing parvovirus capsid structures, this study suggests capsid regions that likely control successful infection, including determinants of receptor attachment, host cell trafficking, and antigenic reactivity. Overall, these observations could impact efforts to design antiviral strategies and vaccines for HBoVs.
Topics: Bocavirus; Capsid; Capsid Proteins; Cryoelectron Microscopy; Human bocavirus; Humans; Imaging, Three-Dimensional; Viral Proteins; Viral Tropism
PubMed: 28331084
DOI: 10.1128/JVI.00261-17 -
Frontiers in Cellular and Infection... 2023The single-stranded DNA virus known as human bocavirus 1 (HBoV-1) is an icosahedral, linear member of the family. In 2005, it was discovered in nasopharyngeal samples... (Review)
Review
The single-stranded DNA virus known as human bocavirus 1 (HBoV-1) is an icosahedral, linear member of the family. In 2005, it was discovered in nasopharyngeal samples taken from kids who had respiratory tract illnesses. The HBoV genome is 4.7-5.7 kb in total length. The HBoV genome comprises three open-reading frames (ORF1, ORF2, and ORF3) that express structural proteins (VP1, VP2, and VP3), viral non-coding RNA, and non-structural proteins (NS1, NS1-70, NS2, NS3, and NP1) (BocaSR). The NS1 and NP1 are crucial for viral DNA replication and are substantially conserved proteins. Replication of the HBoV-1 genome in non-dividing, polarized airway epithelial cells. , HBoV-1 infects human airway epithelial cells that are strongly differentiated or polarized. Young children who have HBoV-1 are at risk for developing a wide range of respiratory illnesses, such as the common cold, acute otitis media, pneumonia, and bronchiolitis. The most common clinical symptoms are wheezing, coughing, dyspnea, and rhinorrhea. After infection, HBoV-1 DNA can continue to be present in airway secretions for months. The prevalence of coinfections is considerable, and the clinical symptoms can be more severe than those linked to mono-infections. HBoV-1 is frequently detected in combination with other pathogens in various reports. The fecal-oral and respiratory pathways are more likely to be used for HBoV-1 transmission. HBoV-1 is endemic; it tends to peak in the winter and spring. This Review summarizes the knowledge on HBoV-1.
Topics: Child; Humans; Animals; Infant; Child, Preschool; Human bocavirus; Respiratory Tract Infections; DNA Replication; Parvoviridae Infections; Virus Replication; DNA, Viral; Genomics; Life Cycle Stages; Viral Structures
PubMed: 37265497
DOI: 10.3389/fcimb.2023.1198127 -
Infection, Genetics and Evolution :... Jun 2022The study aimed to assess the presence and molecular characterization of human bocavirus (HBoV) in recycled water and sewage sludge samples in Thailand. One hundred and...
The study aimed to assess the presence and molecular characterization of human bocavirus (HBoV) in recycled water and sewage sludge samples in Thailand. One hundred and two recycled water and eighty-six sewage sludge samples collected from a wastewater treatment plant were tested for the presence of HBoV using nested PCR with broad-range primer pairs targeting the capsid proteins VP1 and VP2. HBoV DNA was detected in recycled water of 9/102 (8.8%) samples and sewage sludge of 27/86 (31.4%) samples. Based on DNA sequencing and phylogenetic analysis, the HBoV DNA sequences had 98.8-100.0% nucleotide identity to the sequences from HBoV reported globally. Thirty-five HBoV-positive samples were identified to genotypes as the predominant HBoV2; 26 followed by HBoV3; 8 and the rare HBoV4; 1 sample. Concerning recycled water, HBoV2 was detected in 3 (2.9%) and HBoV3 was detected in 5 (4.9%) of all samples. The sewage sludge samples were characterized as HBoV2 in 23 (26.7%), HBoV3 in 3 (3.5%) and HBoV4 in 1 (1.2%) of all samples. The frequency of HBoV detected in recycled water and sewage sludge samples significantly differed in sample type (p-value = 0.007). The findings of three HBoV genotypes in recycled water and sewage sludge emphasized the circulation of the virus in the environment and the potential source of transmission to the community.
Topics: Bocavirus; Human bocavirus; Humans; Parvoviridae Infections; Phylogeny; Sewage; Thailand; Water
PubMed: 35367361
DOI: 10.1016/j.meegid.2022.105276 -
Journal of Virology Mar 2021Human bocavirus 1 (HBoV1) and HBoV2-4 infect children and immunocompromised individuals, resulting in respiratory and gastrointestinal infections, respectively. Using...
Human bocavirus 1 (HBoV1) and HBoV2-4 infect children and immunocompromised individuals, resulting in respiratory and gastrointestinal infections, respectively. Using cryo-electron microscopy and image reconstruction, the HBoV2 capsid structure was determined to 2.7 Å resolution at pH 7.4 and compared to the previously determined HBoV1, HBoV3, and HBoV4 structures. Consistent with previous findings, surface variable region (VR) III of the capsid protein VP3, proposed as a host tissue-tropism determinant, was structurally similar among the gastrointestinal strains HBoV2-4, but differed from HBoV1 with its tropism for the respiratory tract. Towards understanding the entry and trafficking properties of these viruses, HBoV1 and HBoV2 were further analyzed as species representatives of the two HBoV tropisms. Their cell surface glycan-binding characteristics were analyzed, and capsid structures determined to 2.5-2.7 Å resolution at pH 5.5 and 2.6, conditions normally encountered during infection. The data showed that glycans with terminal sialic acid, galactose, GlcNAc or heparan sulfate moieties do not facilitate HBoV1 or HBoV2 cellular attachment. With respect to trafficking, conformational changes common to both viruses were observed at low pH conditions localized to the VP N-terminus under the 5-fold channel, in the surface loops VR-I and VR-V and specific side-chain residues such as cysteines and histidines. The 5-fold conformational movements provide insight into the potential mechanism of VP N-terminal dynamics during HBoV infection and side-chain modifications highlight pH-sensitive regions of the capsid. Human bocaviruses (HBoVs) are associated with disease in humans. However, the lack of an animal model and a versatile cell culture system to study their life cycle limits the ability to develop specific treatments or vaccines. This study presents the structure of HBoV2, at 2.7 Å resolution, determined for comparison to the existing HBoV1, HBoV3, and HBoV4 structures, to enable the molecular characterization of strain and genus-specific capsid features contributing to tissue tropism and antigenicity. Furthermore, HBoV1 and HBoV2 structures determined under acidic conditions provide insight into capsid changes associated with endosomal and gastrointestinal acidification. Structural rearrangements of the capsid VP N-terminus, at the base of the 5-fold channel, demonstrate a disordering of a "basket" motif as pH decreases. These observations begin to unravel the molecular mechanism of HBoV infection and provide information for control strategies.
PubMed: 33472934
DOI: 10.1128/JVI.02329-20 -
Microorganisms May 2023Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and... (Review)
Review
Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and lower respiratory tract infections in adults and children. However, its role as a respiratory pathogen is still not fully understood. It has been reported both as a co-infectious agent (predominantly with respiratory syncytial virus, rhinovirus, parainfluenza viruses, and adenovirus), and as an isolated viral pathogen during respiratory tract infections. It has also been found in asymptomatic subjects. The authors review the available literature on the epidemiology of HBoV, the underlying risk factors associated with infection, the virus's transmission, and its pathogenicity as a single pathogen and in co-infections, as well as the current hypothesis about the host's immune response. An update on different HBoV detection methods is provided, including the use of quantitative single or multiplex molecular methods (screening panels) on nasopharyngeal swabs or respiratory secretions, tissue biopsies, serum tests, and metagenomic next-generations sequencing in serum and respiratory secretions. The clinical features of infection, mainly regarding the respiratory tract but also, though rarely, the gastrointestinal one, are extensively described. Furthermore, a specific focus is dedicated to severe HBoV infections requiring hospitalization, oxygen therapy, and/or intensive care in the pediatric age; rare fatal cases have also been reported. Data on tissue viral persistence, reactivation, and reinfection are evaluated. A comparison of the clinical characteristics of single infection and viral or bacterial co-infections with high or low HBoV rates is carried out to establish the real burden of HBoV disease in the pediatric population.
PubMed: 37317217
DOI: 10.3390/microorganisms11051243 -
Viruses Aug 2023is an expansive genus of the , with a wide range of vertebrate hosts. This study investigates Canine minute virus (CnMV), Rat bocavirus (RBoV), and Porcine bocavirus 1...
is an expansive genus of the , with a wide range of vertebrate hosts. This study investigates Canine minute virus (CnMV), Rat bocavirus (RBoV), and Porcine bocavirus 1 (PBoV1). Both CnMV and PBoV1 have been found in gastrointestinal infections in their respective hosts, with CnMV responsible for spontaneous abortions in dogs, while PBoV has been associated with encephalomyelitis in piglets. The pathogenicity of the recently identified RBoV is currently unknown. To initiate the characterization of these viruses, their capsids structures were determined by cryo-electron microscopy at resolutions ranging from 2.3 to 2.7 Å. Compared to other parvoviruses, the CnMV, PBoV1, and RBoV capsids showed conserved features, such as the channel at the fivefold symmetry axis. However, major differences were observed at the two- and threefold axes. While CnMV displays prominent threefold protrusions, the same region is more recessed in PBoV1 and RBoV. Furthermore, the typical twofold axis depression of parvoviral capsids is absent in CnMV or very small in PBoV and RBoV. These capsid structures extend the structural portfolio for the genus and will allow future characterization of these pathogens on a molecular level. This is important, as no antivirals or vaccines exist for these viruses.
Topics: Animals; Rats; Swine; Dogs; Bocavirus; Cryoelectron Microscopy; Capsid Proteins; Capsid; Parvoviridae Infections
PubMed: 37766206
DOI: 10.3390/v15091799 -
Frontiers in Microbiology 2023
PubMed: 37256056
DOI: 10.3389/fmicb.2023.1194926 -
PloS One 2013Human bocavirus is the second autonomous human parvovirus with assumed pathogenic potential. Other parvoviruses are known to persist and even integrate into the host...
Human bocavirus is the second autonomous human parvovirus with assumed pathogenic potential. Other parvoviruses are known to persist and even integrate into the host genome, eventually contributing to the multi-step development of cancer. Human bocavirus also persists in an unknown percentage of clinically asymptomatic patients in addition to those with primary infection. The aim of the present study was to analyze the role of Human bocavirus in lung and colorectal cancers. Therefore, formalin-fixed, paraffin-embedded, archived tumor samples were screened for Human bocavirus DNA by PCR, Southern blotting, and sequencing. Positive tissues were further subjected to fluorescence in situ hybridization analysis to specifically detect human bocavirus DNA in the infected cells. In total, 11 of the 60 (18.3%) lung and 9 of the 44 (20.5%) colorectal tumors tested positive for human bocavirus DNA by PCR and were confirmed by sequencing and fluorescence in situ hybridization analysis. Thus, human bocavirus DNA is present in the nuclei of infected cells, in either single or multiple copies, and appears to form concatemers. The occurrence of these human bocavirus DNA structures supports the existence of the postulated σ- or rolling-hairpin replication mechanism. Moreover, the fluorescence in situ hybridization patterns inspired the hypothesis that human bocavirus DNA either persists as cccDNA or is integrated into the host genome. This finding suggests that this virus may indirectly contribute to the development of some colorectal and lung cancers, as do other DNA viruses, such as the human hepatitis B virus, or may play an active role in cancer by interacting with the host genome.
Topics: Aged; Colorectal Neoplasms; DNA, Viral; Double-Blind Method; Female; Human bocavirus; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms; Male; Pilot Projects; Polymerase Chain Reaction; Retrospective Studies
PubMed: 23826357
DOI: 10.1371/journal.pone.0068020 -
New Microbes and New Infections Sep 2020Acute bronchiolitis is one of the most common lower respiratory tract infections in children with less than 2 years of age. Nowadays, molecular methods provide an... (Review)
Review
Acute bronchiolitis is one of the most common lower respiratory tract infections in children with less than 2 years of age. Nowadays, molecular methods provide an opportunity to better understand the etiology of bronchiolitis. Several viral agents including Respiratory syncytial virus (RSV), Rhinovirus, Parainfluenza and Human bocavirus (HBoV) are responsible for acute bronchiolitis. There are growing studies on the prevalence of HBoV in patients with bronchiolitis. The present systematic review and meta-analysis were conducted to determine the pooled prevalence of HBoV in the respiratory samples of children with acute bronchiolitis. A literature search was conducted in the databases of PubMed, Scopus and Web of Science to recruit studies reporting the frequency of HBoV in <2-year-old children with acute bronchiolitis from 2005 to 2019. Only studies that used polymerase chain reaction (PCR)-based methods to detect the virus in nasopharyngeal samples were included. A total of 22 studies assessing 6751 cases were analyzed. According to the meta-analysis based on the random-effects model, the overall prevalence of HBoV in children with <2 years old was obtained 13% (95% CI: 0.09-0.17). Additionally, the rates of single (as the sole organism) and mixed (in combination with other viruses) HBoV infections were 4% and 9%, respectively. This study showed a high rate of HBoV detection in children with acute bronchiolitis. This should be considered as part of a diagnostic test panel for respiratory infections in children with bronchiolitis.
PubMed: 32983545
DOI: 10.1016/j.nmni.2020.100736 -
Revue Francophone Des Laboratoires : RFL Nov 2006A new virus has been recently identified by molecular biology technics in respiratory samples collected from young children with respiratory disease. This virus is a new...
A new virus has been recently identified by molecular biology technics in respiratory samples collected from young children with respiratory disease. This virus is a new member of the family and has been classified in the genus. This virus named human bocavirus (HboV) is genetically related to the bovine parvovirus and the canine minus virus that belong to the Bocavirus genus. Recent studies conducted in different countries showed that this virus is found in 3 to 10 % of children with respiratory disease worldwide with no real seasonal distribution and that it is frequently associated with other respiratory pathogens. Genetic analysis indicated that this virus probably includes only one type. The clinical signs are not different from those caused by other respiratory viruses. The exact role played by this virus in human diseases needs to be further investigated.
PubMed: 32288801
DOI: 10.1016/S1773-035X(06)80573-3