儿童急性呼吸道博卡病毒感染

了解博卡病毒(Human Bocavirus,HBoV)在我国儿童急性呼吸道疾病中的感染情况。采用PCR扩增的方法对2005年10月~2006年1月收集的72例急性呼吸道感染的住院儿童鼻咽抽吸物(nasopharyngeal aspirates,NPA)进行了HBoV基因检测。将PCR阳性产物进行TA克隆,测序,并将所测序列与GenBank中HBoV序列进行比较分析。72份标本中共检测到6份HBoV阳性扩增产物,阳性率为8.3%(6/72),该6例HBoV阳性患儿临床均有肺炎或支气管肺炎症状。由此可以初步看出HBoV可能也是儿童急性呼吸道感染中较为重要的一个病原,且可能与儿童急性下呼吸道感染存在相关性。     

Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009–2010, 2011–2012, and 2013–2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1–2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.     

Detection of human bocavirus mRNA in respiratory secretions correlates with high viral load and concurrent diarrhea

Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>10⁸ copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections.     

High Human Bocavirus Viral Load Is Associated with Disease Severity in Children under Five Years of Age

Human bocavirus (HBoV) is a parvovirus and detected worldwide in lower respiratory tract infections (LRTIs), but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses. To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity, we performed a 3-year prospective study of HBoV in healthy controls, outpatients and inpatients under five years of age with X-ray diagnosed LRTIs. Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4. Nasopharyngeal swabs from healthy controls and serum samples and stools from inpatients were also tested for HBoV1-4 by real time PCR. Viral loads were determined by quantitative real time PCR in all HBoV positive samples. HBoV1 was detected in 7.0% of inpatients, with annual rates of 5.1%, 8.0% and 4.8% in 2010, 2011 and 2012, respectively. Respiratory syncytial virus (RSV) subtype A was the most frequent co-infection detected; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations. High HBoV viral loads (>10⁶ copies/ml) were significantly more frequent in inpatients and outpatients than in healthy controls. There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus. In summary, our data suggest that HBoV1 can cause LRTIs, but symptomatic HBoV infection is only observed in the context of high viral load.     

Bocavirus episome in infected human tissue contains non-identical termini

Human bocaviruses (HBoV) are highly prevalent human infections whose pathogenic potential remains unknown. Recent identification of the first non-human primate bocavirus [1] in captive gorillas raised the possibility of the persistent nature of bocavirus infection. To characterize bocavirus infection in humans, we tested intestinal biopsies from 22 children with gastrointestinal disease for the presence of HBoV DNA. Four HBoV-positive tissue samples were analyzed to determine whether viral DNA was present in the linear genomic, the episomal closed circular or the host genome-integrated form. Whereas one tissue sample positive for HBoV3 contained the episomal form (HBoV3-E1), none had the genome-integrated form. The complete genome sequence of HBoV3-E1 contains 5319 nucleotides of which 513 represent the non-coding terminal sequence. The secondary structure of HBoV3-E1 termini suggests several conserved and variable features among human and animal bocaviruses. Our observation that HBoV genome exists as head-to-tail monomer in infected tissue either reflects the likely evolution of alternative replication mechanism in primate bocaviruses or a mechanism of viral persistence in their host. Moreover, we identified the HBoV genomic terminal sequences that will be helpful in developing reverse genetic systems for these widely prevalent parvoviruses. Significance: HBoV have been found in healthy human controls as well as individuals with respiratory or gastrointestinal disease. Our findings suggest that HBoV DNA can exist as episomes in infected human tissues and therefore can likely establish persistent infection in the host. Previous efforts to grow HBoV in cell culture and to develop reverse genetic systems have been unsuccessful. Complete genomic sequence of the HBoV3 episome and its genomic termini will improve our understanding of HBoV replication mechanism and its pathogenesis.     

Detection of human bocavirus and human metapneumovirus by real-time PCR from patients with respiratory symptoms in Southern Brazil

The introduction of newer molecular methods has led to the discovery of new respiratory viruses, such as human metapneumovirus (hMPV) and human bocavirus (hBoV), in respiratory tract specimens. We have studied the occurrence of hMPV and hBoV in the Porto Alegre (PA) metropolitan area, one of the southernmost cities of Brazil, evaluating children with suspected lower respiratory tract infection from May 2007-June 2008. A real-time polymerase chain reaction method was used for amplification and detection of hMPV and hBoV and to evaluate coinfections with respiratory syncytial virus (RSV), influenza A and B, parainfluenza 1, 2 and 3, human rhinovirus and human adenovirus. Of the 455 nasopharyngeal aspirates tested, hMPV was detected in 14.5% of samples and hBoV in 13.2%. A unique causative viral agent was identified in 46.2% samples and the coinfection rate was 43.7%. For hBoV, 98.3% of all positive samples were from patients with mixed infections. Similarly, 84.8% of all hMPV-positive results were also observed in mixed infections. Both hBoV and hMPV usually appeared with RSV. In summary, this is the first confirmation that hMPV and hBoV circulate in PA; this provides evidence of frequent involvement of both viruses in children with clinical signs of acute viral respiratory tract infection, although they mainly appeared as coinfection agents.     

南京地区2010～2011年度呼吸道感染患儿腺病毒的流行病学研究

本研究为了解南京地区儿童腺病毒(ADV)感染的流行特点及型别,收集2010年8月至2011年7月南京医科大学附属南京儿童医院住院及门诊呼吸道感染患儿的鼻咽抽吸物(NPA)及咽拭子(NPS)共644例,采用巢氏聚合酶链反应法(Nested-PCR)检测ADV hexon基因,将阳性PCR扩增产物进行测序、同源性和进化分析。同时对12种其他呼吸道相关病毒进行PCR检测,包括人博卡病毒(HBoV),呼吸道合胞病毒(RSV),人鼻病毒(HRV),副流感病毒1～4型(PIV1-4),流感病毒A和B(IFVA/B),人偏肺病毒(HMPV),冠状病毒NL63和HKU1(HCoV-NL63和HCoV-HKU1)。结果显示:644例标本中共检出ADV阳性扩增产物171份,检出率为26.55%,3型120例(70.18%,120/171),7型16例(9.36%,16/171),1型12例(7.02%,12/171),2型10例(5.85%,10/171),5型6例(3.51%,6/171),6型3例(1.75%,3/171),57型3例(1.75%,3/171),41型1例(0.58%,1/171)。ADV感染呈全年散发,其发病高峰主要在4～7月。以7岁以下儿童多见(96.49%)。171例ADV感染患儿中有99例(57.89%)存在混合感染,其中以呼吸道合胞病毒(RSV)、人鼻病毒(HRV)多见。ADV阳性患儿诊断以下呼吸道感染为主(63.16%),肺炎占30.41%。结论:ADV是2010年8月到2011年7月南京地区儿童呼吸道感染的重要病原之一,其优势流行株为3型,长期监测其流行型别具有重要意义。     

High viral load of human bocavirus correlates with duration of wheezing in children with severe lower respiratory tract infection

Background

Human bocavirus (HBoV) is a newly discovered parvovirus and increasing evidences are available to support its role as an etiologic agent in lower respiratory tract infection (LRTI). The objective of this study is to assess the impact of HBoV viral load on clinical characteristics in children who were HBoV positive and suffered severe LRTI.

Methods

Lower respiratory tract aspirates from 186 hospitalized children with severe LRTI were obtained by bronchoscopy. HBoVs were detected by real-time PCR and other 10 infectious agents were examined using PCR and/or direct fluorescent assay.

Results

Thirty-one patients (24.6%) were tested positive for HBoV in the respiratory tract aspirates. Fifteen samples had a high viral load (>10⁴ copies/mL) and the other sixteen samples had a low viral load (<10⁴ copies/mL). The duration of presented wheezing and hospitalization was longer in children with high viral load of HBoV than that in children with low viral load. The days of wheezing showed a correlation with viral load of HBoV.

Conclusion

We confirmed that HBoV was frequently detected in patients with severe LRTI. Wheezing was one of the most common symptoms presented by patients with positive HBoV. A high HBoV viral load could be an etiologic agent for LRTI, which led to more severe lower respiratory tract symptom, longer duration of wheezing and hospitalization.     

人类博卡病毒HBoV1基因组克隆及启动子活性分析

人类博卡病毒 (Human bocavirus,HBoV) 是继细小病毒B19之后,第2个被发现可引起人类疾病的细小病毒。通过PCR扩增方法从患有下呼吸道感染的患儿痰液中鉴定HBoV,以鉴定的阳性样本为模板,利用分子生物学方法构建病毒基因组克隆并进行序列分析。2007年10月?2009年3月从湖北省妇幼保健院共收集941例下呼吸道感染患儿的痰液标本,检测到33份HBoV阳性样品,阳性率为3.51％ (33/941);其中1岁以下婴幼儿患者占阳性样72.7％;构建了含有HBoV中间大片段基因克隆WHL-1,     

Genomic features of the human bocaviruses

The human bocavirus (HBoV) was initially discovered in 2005 as the second pathogenic member of the parvovirus family, next to the human parvovirus B19. HBoV has since been shown to be extremely common worldwide and to cause a systemic infection in small children often resulting in respiratory disease. Three more, presumably enteric, human bocaviruses (HBoV2-4) have been identified in stool samples. Parvoviruses are assumed to replicate via their genomic terminal hairpin-like structures in a so-called 'rolling-hairpin model'. These terminal sequences have recently been partially identified in head-to-tail HBoV-PCR amplicons from clinical samples, and are most likely hybrid relics of HBoV's predecessors, namely bovine parvovirus 1 on the left-hand side and minute virus of canines on the right, shown for the first time in this article. Thereby, the replication model postulated for HBoV remains questionable as the occurrence of head-to-tail sequences is not a typical feature of the rolling-hairpin replication model. However, such episomes can also be persistent storage forms of the genome.     

Characteristic systemic cytokine responses in children with human bocavirus‐positive lower respiratory tract infection

To investigate systemic cytokine responses in human bocavirus (HBoV)‐associated lower respiratory tract infection, serum cytokine profiles were analyzed in HBoV positive‐children (n = 14) using multiplex immunoassay. Concentrations of TNF‐α, IL‐2, IL‐5 and IL‐8 on admission were significantly different from those of respiratory syncytial virus‐positive children (n = 28). This unique cytokine response might partly explain some characteristic clinical features of HBoV‐associated respiratory infection.     

Surveillance and Genome Analysis of Human Bocavirus in Patients with Respiratory Infection in Guangzhou, China

Human bocavirus (HBoV) is a novel parvovirus associated with respiratory tract diseases and gastrointestinal illness in adult and pediatric patients throughout the world. To investigate the epidemiological and genetic variation of HBoV in Guangzhou, South China, we screened 3460 throat swab samples from 1686 children and 1774 adults with acute respiratory infection symptoms for HBoV between March 2010 and February 2011, and analyzed the complete genome sequence of 2 HBoV strains. Specimens were screened for HBoV by real-time PCR and other 6 common respiratory viruses by RT-PCR or PCR. HBoV was detected in 58 (1.68%) out of 3460 samples, mostly from pediatric patients (52/58) and inpatient children (47/58). Six adult patients were detected as HBoV positive and 5 were emergency cases. Of these HBoV positive cases, 19 (32.76%) had co-pathogens including influenza virus (n = 5), RSV (n = 5), parainfluenza (n = 4), adenovirus (n = 1), coronavirus (n = 7). The complete genome sequences of 2 HBoVs strains (Genbank no. {"type":"entrez-nucleotide","attrs":{"text":"JN794565","term_id":"361064618","term_text":"JN794565"}}JN794565 and {"type":"entrez-nucleotide","attrs":{"text":"JN794566","term_id":"361064623","term_text":"JN794566"}}JN794566) were analyzed. Phylogenetic analysis showed that the 2 HBoV strains were HBoV1, and were most genetically close to ST2 (GenBank accession number DQ0000496). Recombination analysis confirmed that HBoV strain GZ9081 was an intra–genotype recombinant strain among HBoV1 variants.     

Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways

Human bocavirus 1 (HBoV1) belongs to the genus Bocaparvovirus of the Parvoviridae family, and is an emerging human pathogenic respiratory virus. In vitro, HBoV1 infects well-differentiated/polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). Although it is well known that autonomous parvovirus replication depends on the S phase of the host cells, we demonstrate here that the HBoV1 genome amplifies efficiently in mitotically quiescent airway epithelial cells of HAE-ALI cultures. Analysis of HBoV1 DNA in infected HAE-ALI revealed that HBoV1 amplifies its ssDNA genome following a typical parvovirus rolling-hairpin DNA replication mechanism. Notably, HBoV1 infection of HAE-ALI initiates a DNA damage response (DDR) with activation of all three phosphatidylinositol 3-kinase–related kinases (PI3KKs). We found that the activation of the three PI3KKs is required for HBoV1 genome amplification; and, more importantly, we identified that two Y-family DNA polymerases, Pol η and Pol κ, are involved in HBoV1 genome amplification. Overall, we have provided an example of de novo DNA synthesis (genome amplification) of an autonomous parvovirus in non-dividing cells, which is dependent on the cellular DNA damage and repair pathways.     

The Human Bocavirus Is Associated with Some Lung and Colorectal Cancers and Persists in Solid Tumors

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.     

Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia

Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections. In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface. Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1. Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis.     

Detection of KI polyomavirus and WU polyomavirus DNA by real-time polymerase chain reaction in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues

Polyomaviruses KI (KIPyV) and WU (WUPyV) were detected from 7 (3.0%) and 38 (16.4%) of 232 children with respiratory tract infections by real-time PCR. The rates of infection by KIPyV and WUPyV alone were 3 of 7 (42.9%) and 20 of 38 (52.6%), respectively. In the other samples, various viruses (human respiratory syncytial virus, human metapneumovirus, human rhinovirus, parainfluenza virus 1 and human bocavirus) were detected simultaneously. One case was positive for KIPyV, WUPyV and hMPV. There was no obvious difference in clinical symptoms between KIPyV-positive and WUPyV-positive patients with or without coinfection. KIPyV was detected in one of 30 specimens of lung tissue (3.3%). Neither of the viruses was detected in 30 samples of lung adenocarcinoma tissue.     

Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia

Objective

Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance.

Methods

Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed.

Results

High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control.

Conclusions

With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.     

Detection and quantitative analysis of human bocavirus associated with respiratory tract infection in Osaka City,Japan

HBoV was initially identified in patients with RTI in 2005. Since its discovery, there have been continual reports concerning HBoV detection and its prevalence. In this study of clinical specimens from young children, real‐time PCR was undertaken to examine whether HBoV infection is associated with RTI and to support quantitative analysis of HBoV in these patients. In all, 376 specimens were collected from patients with RTI during April 2006–October 2008. Analyses revealed HBoV in 59 specimens (15.7%). Of HBoV‐positive patients, children under the age of 3 years comprised 94.9%. Of the HBoV‐positive samples, 47.5% were codetected with other respiratory viruses (dual infection, 27; triple infection, 1). During the study period, the numbers and rate of detection of HBoV were high mainly around May. Statistical analyses showed that the detection rate of HBoV during April–June was higher than during other months. Moreover, the viral load was greater in subjects with infection with HBoV alone than in subjects with mixed respiratory viral infections. Considering these results together, HBoV is probably associated with RTI in young children. However, the pathogenesis of this infection and the importance of the high rate of co‐infection remain uncertain. Additional epidemiologic information and further analyses are necessary to clarify the virological characteristics and the linkage of HBoV to disease.     

Human Bocaviruses Are Not Significantly Associated with Gastroenteritis: Results of Retesting Archive DNA from a Case Control Study in the UK

Gastroenteritis is a common illness causing considerable morbidity and mortality worldwide. Despite improvements in detection methods, a significant diagnostic gap still remains. Human bocavirus (HBoV)s, which are associated with respiratory infections, have also frequently been detected in stool samples in cases of gastroenteritis, and a tentative association between HBoVs, and in particular type-2 HBoVs, and gastroenteritis has previously been made. The aim of this study was to determine the role of HBoVs in gastroenteritis, using archived DNA samples from the case-control Infectious Intestinal Disease Study (IID). DNA extracted from stool samples from 2,256 cases and 2,124 controls were tested for the presence of HBoV DNA. All samples were screened in a real time PCR pan-HBoV assay, and positive samples were then tested in genotype 1 to 3-specific assays. HBoV was detected in 7.4% but no significantly different prevalence was observed between cases and controls. In the genotype-specific assays 106 of the 324 HBoV-positive samples were genotyped, with HBoV-1 predominantly found in controls whilst HBoV-2 was more frequently associated with cases of gastroenteritis (p<0.01). A significant proportion of HBoV positives could not be typed using the type specific assays, 67% of the total positives, and this was most likely due to low viral loads being present in the samples. However, the distribution of the untyped HBoV strains was no different between cases and controls. In conclusion, HBoVs, including HBoV-2 do not appear to be a significant cause of gastroenteritis in the UK population.     

The changing face of pediatric respiratory tract infections: how human metapneumovirus and human bocavirus fit into the overall etiology of respiratory tract infections in young children

Lower respiratory tract infections are one of the leading causes of morbidity and mortality in children worldwide. Recent technological advances in the field of molecular biology have allowed virologists to detect many previously undetected viral pathogens. Two of these, human metapneumovirus (hMPV) and human bocavirus (HBoV), are of particular clinical interest to pediatric health care providers. This review discusses the most common viral respiratory infections in children, explores the role of newly discovered respiratory pathogens, and describes techniques for the diagnosis of viral respiratory infections.