Human Bocavirus as the Cause of a Life-Threatening Infection

Uršič, Tina; Steyer, Andrej; Kopriva, Silvester; Kalan, Gorazd; Krivec, Uroš; Petrovec, Miroslav

doi:10.1128/jcm.02362-10

Cited by 78 publications

(72 citation statements)

References 23 publications

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“…However, while HBoV-1 infection is frequent and shedding may be long-lasting in infants and toddlers, primary HBoV-1 infections are comparably rare among 4-year-olds, making such a coincidence unlikely. The presentation was very similar to a recently published case also linked to HBoV-1 (12). Thus, we find it likely that the observed primary HBoV-1 infection did cause the symptoms.…”

Section: Case Reportsupporting

confidence: 87%

“…Thus, blood testing is crucial for studying HBoV-1 and disease, and new studies applying adequate diagnostic testing are urgently required. Ursic et al (12) recently reported on a 20-month-old child who presented with acute bronchiolitis that developed into a severe course characterized by pneumothorax, pneumomediastinum, and respiratory failure with air-leak syndrome, a clinical course very similar to that of the present case. The solid diagnostic workup included electron microscopy and monitoring of HBoV-1 DNA in upper and lower respiratory secretions and plasma (12).…”

Section: Case Reportsupporting

confidence: 76%

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Life-Threatening Respiratory Tract Disease with Human Bocavirus-1 Infection in a 4-Year-Old Child

et al. 2012

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The disease spectrum associated with human bocavirus-1 infection remains to be fully defined. We report a case of bocavirus-1-associated bronchiolitis, leading to severe respiratory failure and extracorporeal membrane oxygenation in a 4-year-old child, and suggest blood testing for human bocavirus-1 in children with severe respiratory tract infection. CASE REPORTT he patient was a 4-year-old girl, prematurely born in gestational week 29. She had an ordinary upbringing with mild infection-associated wheezing and was hospitalized once at 1 year of age for wheezing. She had no continuous medication but was prescribed albuterol inhalation as needed. The disease episode started rather suddenly with mild dyspnea. Albuterol inhalation gave no amelioration, and this prompted two outpatient visits to the emergency ward of the local hospital on the first 2 days of the disease. Fever (38.2°C) was noted, and she was given albuterol and budesonide inhalations and oral (p.o.) penicillin V with moderate effect. During the second night of the disease, her respiration deteriorated with heavy dyspnea and wheezing, and she returned to the hospital for a third time. Because of severe airway constriction she was now referred to a pediatrics clinic in a secondary hospital. A chest X-ray showed subcutaneous emphysema, pneumomediastinum, and left-sided pneumothorax, which are known complications of severe wheezing in children (5), as well as bilateral minor infiltrates. She was given intravenous (i.v.) cefotaxime and erythromycin. Tracheal intubation was performed and bilateral chest tubes were inserted without an improvement in oxygen saturation. Ventilating the patient was problematic, requiring a peak inspiratory pressure up to 55 cm H 2 O to maintain tidal volumes of 9 ml/kg. At this point the patient had a partial CO 2 pressure (pCO 2 ) of 11.0 kPa (82 mm Hg), and the extracorporeal membrane oxygenation (ECMO) unit at Karolinska University Hospital was contacted. The patient was cannulated for venovenous (VV)-ECMO (15F double-lumen Origen cannulae) locally and transferred to Karolinska in Stockholm. The patient was stabilized, but the ECMO treatment was complicated by cannula perforation of the right atrium and an acute thoracotomy had to be performed. Her respiration improved gradually over the following days. She could be removed from ECMO support after 2 days and extubated after 5 days. The girl made a full recovery and was healthy on follow-up.At the start of ECMO treatment, plasma C-reactive protein was 37 mg/liter and the white blood cell count was 8.0 ϫ 10 9 /liter. Bacterial and fungal cultures from tracheal aspirate, urine, and blood collected on the first and second day of ECMO treatment were negative, including cultures for Legionella pneumophila (tracheal aspirate) and Bordetella pertussis (nasopharyngeal swab). However, the samples were obtained after initiation of antibiotic therapy. An immunofluorescence test for respiratory syncytial virus (RSV) on a nasopharyngeal sample made at the secondary hospital was negative...

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Section: Case Reportsupporting

confidence: 87%

Section: Case Reportsupporting

confidence: 76%

Life-Threatening Respiratory Tract Disease with Human Bocavirus-1 Infection in a 4-Year-Old Child

et al. 2012

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“…HBoV1 causes lower respiratory tract infections, especially in infants less than 2 years old (3)(4)(5)(6)(7). Severe and deadly cases associated with high viral load, anti-HBoV1 IgM antibody detection, or increased IgG antibody production have been documented (7)(8)(9). In vitro, HBoV1 infects polarized primary human airway epithelium cultured at an airliquid interface (HAE-ALI) (10) and causes damage to the airway epithelium (11)(12)(13).…”

mentioning

confidence: 99%

Identification and Functional Analysis of Novel Nonstructural Proteins of Human Bocavirus 1

Shen

Deng

Zou

et al. 2015

J Virol

102

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Human bocavirus 1 (HBoV1) is a single-stranded DNA parvovirus that causes lower respiratory tract infections in young children worldwide. In this study, we identified novel splice acceptor and donor sites, namely, A1= and D1=, in the large nonstructural protein (NS1)-encoding region of the HBoV1 precursor mRNA. The novel small NS proteins (NS2, NS3, and NS4) were confirmed to be expressed following transfection of an HBoV1 infectious proviral plasmid and viral infection of polarized human airway epithelium cultured at an air-liquid interface (HAE-ALI). We constructed mutant pIHBoV1 infectious plasmids which harbor silent mutations (sm) smA1= and smD1= at the A1= and D1= splice sites, respectively. The mutant infectious plasmids maintained production of HBoV1 progeny virions at levels less than five times lower than that of the wild-type plasmid. Importantly, the smA1= mutant virus that does not express NS3 and NS4 replicated in HAE-ALI as effectively as the wild-type virus; however, the smD1= mutant virus that does not express NS2 and NS4 underwent an abortive infection in HAE-ALI. Thus, our study identified three novel NS proteins, NS2, NS3, and NS4, and suggests an important function of the NS2 protein in HBoV1 replication in HAE-ALI. IMPORTANCEHuman bocavirus 1 infection causes respiratory diseases, including acute wheezing in infants, of which life-threatening cases have been reported. In vitro, human bocavirus 1 infects polarized human bronchial airway epithelium cultured at an air-liquid interface that mimics the environment of human lower respiratory airways. Viral nonstructural proteins are often important for virus replication and pathogenesis in infected tissues or cells. In this report, we identified three new nonstructural proteins of human bocavirus 1 that are expressed during infection of polarized human bronchial airway epithelium. Among them, we proved that one nonstructural protein is critical to the replication of the virus in polarized human bronchial airway epithelium. The creation of nonreplicating infectious HBoV1 mutants may have particular utility in vaccine development for this virus. Human bocavirus 1 (HBoV1) belongs to genus Bocaparvovirus of the Parvoviridae family (1, 2). HBoV1 causes lower respiratory tract infections, especially in infants less than 2 years old (3-7). Severe and deadly cases associated with high viral load, anti-HBoV1 IgM antibody detection, or increased IgG antibody production have been documented (7-9). In vitro, HBoV1 infects polarized primary human airway epithelium cultured at an airliquid interface (HAE-ALI) (10) and causes damage to the airway epithelium (11-13). Currently, no specific treatments for HBoV1 infection are available for hospitalized infants.The RNA transcription profiles of three species in the genus Bocaparvovirus, i.e., canine minute virus (CnMV/MVC) (14), bovine parvovirus type 1 (BPV1) (15), and HBoV1 (10), have been studied during virus infection. These species share similarities in their gene expression, with distinguishing featur...

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“…HBoV has also been reported to associate with acute wheezing and encephalitis (31,32). Two cases of life-threatening HBoV infection have been described recently, suggesting that HBoV most likely plays a role in severe and lethal diseases (33,34). The genome of HBoV contains three open reading frames, encoding four proteins, among which VP2 shares the same sequence with VP1, and only differs in the N-terminal extension (35).…”

mentioning

confidence: 99%

Human Bocavirus VP2 Upregulates IFN-β Pathway by Inhibiting Ring Finger Protein 125–Mediated Ubiquitination of Retinoic Acid–Inducible Gene-I

Luo

Zhang

Zheng

et al. 2013

The Journal of Immunology

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Precise regulation of innate immunity is crucial for maintaining optimal immune responses against infections. Whereas positive regulation of IFN signaling elicits rapid type I IFNs, negative regulation is equally important in preventing the production of superfluous IFNs that can be hazardous to the host. The positive regulators of IFN pathway are known to be the main targets of viruses to antagonize the innate immune system. Whether viruses target the negative regulators of IFN pathway remains to be fully investigated. In this study, we report that the structural protein VP2 of human Bocavirus modulates IFN pathway by targeting the ring finger protein 125 (RNF125), a negative regulator of type I IFN signaling, which conjugates Lys48-linked ubiquitination to retinoic acid–inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. VP2 not only upregulated Sendai virus (SeV)–induced IFNB promoter activity, but also enhanced SeV-induced IFN-β production at both mRNA and protein levels. In agreement, the level of Ser396-phosphorylated IFN regulatory factor 3 stimulated by SeV was enhanced in the presence of VP2. Furthermore, VP2 was demonstrated to physically interact with RNF125, resulting in the reduction of RNF125-mediated ubiquitination and proteasome-dependent degradation of RIG-I. Additional study indicated that endogenous RIG-I degradation was decreased in VP2-expressing cells. Our study delineates a unique phenomenon for aberrant activation of IFN regulatory factor 3 pathway and may represent a new mechanism underlying viral manipulation of the host immune system.

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Human Bocavirus as the Cause of a Life-Threatening Infection

Cited by 78 publications

References 23 publications

Life-Threatening Respiratory Tract Disease with Human Bocavirus-1 Infection in a 4-Year-Old Child

Life-Threatening Respiratory Tract Disease with Human Bocavirus-1 Infection in a 4-Year-Old Child

Identification and Functional Analysis of Novel Nonstructural Proteins of Human Bocavirus 1

Human Bocavirus VP2 Upregulates IFN-β Pathway by Inhibiting Ring Finger Protein 125–Mediated Ubiquitination of Retinoic Acid–Inducible Gene-I

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