Co-infection with porcine bocavirus and porcine circovirus 2 affects inflammatory cytokine production and tight junctions of IPEC-J2 cells.

Porcine bocavirus (PBoV) has a high prevalence in both healthy and diseased swine around the world. It was recently reported that PBoV and porcine circovirus type 2 (PCV2)-which contribute to porcine diarrheal disease-have a high rate of co-infection. To clarify the pathogenesis of PBoV, we examined the co-infection rate and effects of these two pathogens in IPEC-J2 porcine intestinal enterocytes. Both single and co-infection had cytopathic effects in IPEC-J2 cells. The apoptosis and proliferation rates of cells infected with both viruses did not differ significantly from those of cells infected with either one alone. PBoV and PCV2 induced the upregulation of inflammatory cytokines and the downregulation of the tight junction proteins occludin and claudin 1 in the early stage of infection, leading to destruction of epithelial barrier integrity and enhanced cytotoxicity. These findings provide insight into the pathogenic mechanisms of PBoV and PCV2 and a basis for developing effective strategies to prevent the spread of gastrointestinal diseases in pigs and other livestock.

New and emerging pathogens in canine infectious respiratory disease.

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Bocavirus infection induces a DNA damage response that facilitates viral DNA replication and mediates cell death.

Minute virus of canines (MVC) is an autonomous parvovirus that replicates efficiently without helper viruses in Walter Reed/3873D (WRD) canine cells. We previously showed that MVC infection induces mitochondrion-mediated apoptosis and G(2)/M-phase arrest in infected WRD cells. However, the mechanism responsible for these effects has not been established. Here, we report that MVC infection triggers a DNA damage response in infected cells, as evident from phosphorylation of H2AX and RPA32. We discovered that both ATM (ataxia telangiectasia-mutated kinase) and ATR (ATM- and Rad3-related kinase) were phosphorylated in MVC-infected WRD cells and confirmed that ATM activation was responsible for the phosphorylation of H2AX, whereas ATR activation was required for the phosphorylation of RPA32. Both pharmacological inhibition of ATM activation and knockdown of ATM in MVC-infected cells led to a significant reduction in cell death, a moderate correction of cell cycle arrest, and most importantly, a reduction in MVC DNA replication and progeny virus production. Parallel experiments with an ATR-targeted small interfering RNA (siRNA) had no effect. Moreover, we identified that this ATM-mediated cell death is p53 dependent. In addition, we localized the Mre11-Rad50-Nbs1 (MRN) complex, the major mediator as well as a substrate of the ATM-mediated DNA damage response pathway to MVC replication centers during infection, and show that Mre11 knockdown led to a reduction in MVC DNA replication. Our findings are the first to support the notion that an autonomous parvovirus is able to hijack the host DNA damage machinery for its own replication and for the induction of cell death.

Production, characterisation and applications of monoclonal antibodies to two novel porcine bocaviruses from swine in Northern Ireland.

The production, preliminary characterisation and applications of monoclonal antibodies (mAbs) against two novel swine bocaviruses isolated in cell culture from swine in Northern Ireland are described. Of the 17 stable final clones produced, four were characterised. All were of the IgG2a isotype and showed no cross-reactivity with either bocavirus strain. Partial neutralisation was observed with PBoV4 mAbs and homologous virus. The two mAbs selected for use in antigen-detecting ELISAs were successful in highlighting those fractions containing infectious virus within sucrose gradients. This is the first report of the production of specific reagents that will prove useful in the study of the biology of these viruses and swine bocavirus-associated diseases.

From a case-control survey to a diagnostic viral gastroenteritis panel for testing of general practitioners' patients.

OBJECTIVE: To evaluate the pathogenicity of a broad range of 11 possible gastroenteritis viruses, by means of statistical relationships with cases vs. controls, or Ct-values, in order to establish the most appropriate diagnostic panel for our general practitioner (GP) patients in the Netherlands (2010-2012). METHODS: Archived stool samples from 1340 cases and 1100 controls were retested using internally controlled multiplex real-time PCRs for putative pathogenic gastroenteritis viruses: adenovirus, astrovirus, bocavirus, enterovirus, norovirus GI and GII, human parechovirus, rotavirus, salivirus, sapovirus, and torovirus. RESULTS: The prevalence of any virus in symptomatic cases and asymptomatic controls was 16.6% (223/1340) and 10.2% (112/1100), respectively. Prevalence of astrovirus (adjusted odds ratio (aOR) 10.37; 95% confidence interval (CI) 1.34-80.06) and norovirus GII (aOR 3.10; CI 1.62-5.92) was significantly higher in cases versus controls. Rotavirus was encountered only in cases. We did not find torovirus and there was no statistically significant relationship with cases for salivirus (aOR 1,67; (CI) 0.43-6.54)), adenovirus non-group F (aOR 1.20; CI 0.75-1.91), bocavirus (aOR 0.85; CI 0.05-13.64), enterovirus (aOR 0.83; CI 0.50-1.37), human parechovirus (aOR 1.61; CI 0.54-4.77) and sapovirus (aOR 1.15; CI 0.67-1.98). Though adenovirus group F (aOR 6.37; CI 0.80-50.92) and norovirus GI (aOR 2.22, CI: 0.79-6.23) are known enteropathogenic viruses and were more prevalent in cases than in controls, this did not reach significance in this study. The Ct value did not discriminate between carriage and disease in PCR-positive subjects. CONCLUSIONS: In our population, diagnostic gastroenteritis tests should screen for adenovirus group F, astrovirus, noroviruses GI and GII, and rotavirus. Case-control studies as ours are lacking and should also be carried out in populations from other epidemiological backgrounds.

Emerging viruses in transplantation.

PURPOSE OF REVIEW: Several viruses have recently gained importance for the transplant recipient. The purpose of this review is to give an update on emerging viruses in transplantation. RECENT FINDINGS: BK virus-associated nephropathy (BKVAN) causes graft loss after kidney transplantation. Immunosuppression lowering strategies have now been shown to have benefit in decreasing the incidence of BKVAN. Guidelines for screening, prevention, and therapy have also been developed. Another polyomavirus, JC virus, is a cause of progressive multifocal leukoencephalopathy and has also gained prominence due to the increasing use of monoclonal antibodies in transplant recipients. The significance of human herpesvirus-6 and -7 continues to be debated in the literature, and new data is available on their association with clinical disease. Finally, newly discovered respiratory viruses, such as human metapneumovirus, bocavirus, KI and WU viruses, have also been described in transplant recipients. Human metapneumovirus appears to cause significant respiratory disease whereas the significance of bocavirus, KI and WU viruses in transplant recipients remains uncertain. SUMMARY: Viral infections, such as polyomaviruses, human herpesvirus-6 and -7 and respiratory viruses, are emerging as causes of significant disease in transplantation. Antiviral options for these viruses are limited, and decreasing immunosuppression is the cornerstone of therapy.

Prevalence of respiratory viruses using polymerase chain reaction in children with wheezing, a systematic review and meta-analysis.

INTRODUCTION: Wheezing is a major problem in children, and respiratory viruses are often believed to be the causative agent. While molecular detection tools enable identification of respiratory viruses in wheezing children, it remains unclear if and how these viruses are associated with wheezing. The objective of this systematic review is to clarify the prevalence of different respiratory viruses in children with wheezing. METHODS: We performed an electronic in Pubmed and Global Index Medicus on 01 July 2019 and manual search. We performed search of studies that have detected common respiratory viruses in children ≤18 years with wheezing. We included only studies using polymerase chain reaction (PCR) assays. Study data were extracted and the quality of articles assessed. We conducted sensitivity, subgroup, publication bias, and heterogeneity analyses using a random effects model. RESULTS: The systematic review included 33 studies. Rhinovirus, with a prevalence of 35.6% (95% CI 24.6-47.3, I2 98.4%), and respiratory syncytial virus, at 31.0% (95% CI 19.9-43.3, I2 96.4%), were the most common viruses detected. The prevalence of other respiratory viruses was as follows: human bocavirus 8.1% (95% CI 5.3-11.3, I2 84.6%), human adenovirus 7.7% (95% CI 2.6-15.0, I2 91.0%), influenza virus6.5% (95% CI 2.2-12.6, I2 92.4%), human metapneumovirus5.8% (95% CI 3.4-8.8, I2 89.0%), enterovirus 4.3% (95% CI 0.1-12.9, I2 96.2%), human parainfluenza virus 3.8% (95% CI 1.5-6.9, I2 79.1%), and human coronavirus 2.2% (95% CI 0.6-4.4, I2 79.4%). CONCLUSIONS: Our results suggest that rhinovirus and respiratory syncytial virus may contribute to the etiology of wheezing in children. While the clinical implications of molecular detection of respiratory viruses remains an interesting question, this study helps to illuminate the potential of role respiratory viruses in pediatric wheezing. REVIEW REGISTRATION: PROSPERO, CRD42018115128.

Human bocavirus in children with acute lymphoblastic leukemia.

A new human parvovirus, human bocavirus, has recently been identified in respiratory secretions, feces and serum. It is associated with lower and most likely also upper respiratory tract infections. Most commonly reported symptoms are cough, rhinorrhea, expiratory wheezing and fever, and the virus is preferentially detected in young children. We report three children with acute lymphoblastic leukemia who had acute febrile episodes with concomitant detection of human bocavirus in their respiratory secretions. One of them had five consecutive febrile episodes during 6 months, all associated with the presence of human bocavirus at varying viral loads, suggesting prolonged shedding or reactivation of the virus.

[Etiological structure of influenza and other ARVI in St. Petersburg during epidemic seasons 2012-2016.]

The etiological structure of influenza and other acute respiratory viral infections including their rate of incidence in St. Petersburg and Leningrad region during 4 epidemic seasons has been studied. Seasonality of some respiratory viruses was shown and peaks of circulation of RSV, adenovirus, parainfluenza viruses, rhinovirus, bocavirus, metapneumovirus and coronavirus were marked. The interference of influenza A viruses and RSV, RSV and rhinoviruses was highlighted. A high incidence of adenovirus infection in organized communities and RSV infection in children was revealed.

Etiology and clinical features of viral bronchiolitis in infancy.

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection in infancy. The aim of this review is to present the clinical profile of viral bronchiolitis, the different culprit viruses and the disease severity in relation to the viral etiology. DATA SOURCES: Databases including PubMed and Google Scholar were searched for articles about the clinical features of bronchiolitis and its viral etiology. The most relevant articles to the scope of this review were analyzed. RESULTS: Currently there are two main definitions for bronchiolitis which are not identical, the European definition and the American one. The most common viral pathogen that causes bronchiolitis is respiratory syncytial virus which was identified in 1955; now many other viruses have been implicated in the etiology of bronchiolitis such as rhinovirus, adenovirus, metapneumovirus, and bocavirus. Several studies have attempted to investigate the correlation of bronchiolitis severity with the type of detected virus or viruses. However, the results were not consitent. CONCLUSIONS: For the time being, the diagnosis of bronchiolitis remains clinical. The isolation of the responsible respiratory pathogens does not seem to confer to the prognosis of the disease severity.

Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013.

BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.

Human bocavirus infections are common in Beijing population indicated by sero-antibody prevalence analysis.

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that was originally detected in the respiratory secretions of children with respiratory infections. This study aimed to learn about the importance of HBoV infections by revealing the prevalence of serum antibodies against HBoV in Beijing population. METHODS: Two batches of serum specimens collected in different periods were tested by Western blotting for specific IgG against HBoV using recombinant VP2 as antigen. RESULTS: Out of 677 serum specimens collected during April 1996 to March 1997, 400 (59.1%) were positive and antibody positive rate for another batch of 141 serum specimens collected in August, 2005 from adults aged from 20 years to over 60 years was 78.7% (111/141). Comparison of the sero-prevalence profiles for serum specimens collected during 1996 - 1997 to those collected in 2005 indicated that the antibody positive rate for specimens collected in 2005 was higher than that of the corresponding age groups collected during 1996 - 1997. CONCLUSIONS: The data suggest that HBoV has been circulating in Beijing population for at least over 10 years, and most of children had been exposed to HBoV by age of 7 years. Higher HBoV antibody positive rate shown in the serum specimens collected in 2005 suggested that infections by HBoV have been increased in Beijing population in recent years.

[Human bocavirus (HBoV)]. / Le bocavirus humain (HBoV).

The human bocavirus (HBoV) has been recently identified by means of molecular screening techniques in respiratory tract secretions from children with acute respiratory tract disease. This virus, which belongs to the Parvoviridae family, has been detected worldwide with a 5 to 10% prevalence among children with upper or lower respiratory tract infections, essentially during the winter period. A seroepidemiological study has shown that almost all the children have antibodies to HBoV by the age of five years, and HBoV infection seems to be rare in adults. HBoV is often detected in association with other respiratory viruses. This virus has also been detected in stools, but its role in gastroenteritis has not been yet established. Virological diagnostic of HBoV infection is based on the detection of viral DNA by PCR. Viral load determination by viral DNA quantitation in respiratory tract secretions could be a tool to differentiate between symptomatic HBoV infection and virus carriage.

Human bocavirus, a newly discovered parvovirus of the respiratory tract.

Human Bocavirus is a newly discovered parvovirus. This virus is the fourth most frequently detected virus among symptomatic children with respiratory infection. Human Bocavirus is present worldwide and is a probable cause of symptomatic respiratory infection, although Koch's postulates are not all fulfilled. In this article, we propose an overview of the main clinical data about this virus, two years after its discovery. In addition, we discuss some hypotheses about its tropism for the lung in young children.