Correlation between nucleotide mutation and viral loads of human bocavirus 1 in hospitalized children with respiratory tract infection

Hao, Rui; Ni, Ke; Xia, Qiuling; Peng, Caijing; Deng, Yu; Zhao, Xiaodong; Fu, Zhou; Liu, Enmei

doi:10.1099/vir.0.047472-0

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…In agreement with others [42], the phylogenetic analysis of this study confirmed the very low degree of variability in the hBoV genomic region encoding proteins that are exposed to the virus surface and are therefore under immunologic pressure. Only 9% (62 codons) of amino acids were found to have at least one change in the VP1/VP2 gene, a finding not substantially different from that reported by Hao et al in a different geographic area [40]. In our study, several amino acid changes were observed in strains circulating in almost all the respiratory seasons.…”

Section: Discussioncontrasting

confidence: 69%

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Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

et al. 2015

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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.

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Section: Discussioncontrasting

confidence: 69%

“…However, mutations associated with increased or reduced replication are rarely reported for hBoV. Recently, Hao et al have reported that few nucleotide changes were correlated with a lower viral load [40]. In the present study, a double mutant (N546H and T590S) was observed in samples with a significantly higher viral load.…”

Section: Discussionsupporting

confidence: 53%

Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

et al. 2015

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“…Amplification of HBoV1 DNA by real-time quantity PCR was performed with the NS1 primers and probe [19,20]. The plasmid amplified target fragment was cloned into the pMD19-T vector (TaKaRa Biotechonology, Dalian, China) and verified by sequencing.…”

Section: Real-time Fluorescence Quantitative Pcr For Hbov1mentioning

confidence: 99%

Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children

et al. 2014

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BackgroundHuman bocavirus is a newly discovered parvovirus. Multiple studies have confirmed the presence of human bocavirus1 (HBoV1) in respiratory tract samples of children. The viral load, presentation of single detection and its role as a causative agent of severe respiratory tract infections have not been thoroughly elucidated.MethodsWe investigated the presence of HBoV1 by quantitative polymerase chain reaction (PCR) of nasopharyngeal aspirate specimens from 1229 children hospitalized for respiratory tract infections. The samples were analyzed for 15 respiratory viruses by PCR and 7 respiratory viruses by viral culture.ResultsAt least one virus was detected in 652 (53.1%) of 1229 children, and two or more viruses were detected in 266 (21.6%) children. HBoV1 was detected in 127 children (10.3%), in which 66/127 (52%) of the cases were the only HBoV1 virus detected. Seasonal variation was observed with a high HBoV1 infection rate in summer. A cutoff value of 107 copies/mL was used to distinguish high and low HBoV1 viral loads in the nasopharyngeal aspirates. High viral loads of HBoV1 were noted predominantly in the absence of other viral agents (28/39, 71.8%) whereas there was primarily co-detection in cases of low HBoV1 viral loads (50/88, 56.8%). There were no differences in the clinical symptoms and severity between HBoV1 single detection and co-detection. In cases of HBoV1 single detection, the high viral load group was more prevalent among children with dyspnea and wheezing than was the low viral load group (42.9% vs. 23.7%, P = 0.036; 60.7% vs. 31.6%, P = 0.018). In clinical severity, a significant difference was recorded (25.0% vs. 5.3%, P = 0.003) between high viral load and low viral load groups. Of the HBoV1 positive patients associated with severe respiratory tract infections, 10/18 (55.6%) patients belonged to the HBoV1 high viral load group, and 7/10 (70%) patients had cases of HBoV1 single detection.ConclusionsHBoV1 at a high viral load is not frequently found in co-detection with other respiratory viruses, and a single detection with a high viral load could be an etiological agent of severe respiratory tract infections.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-424) contains supplementary material, which is available to authorized users.

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“…Sequence analysis showed 11 mutations among which 6 nonsense and 5 sense mutations were found in NS1 ORF (Table 1 ). We also analyzed 47 different strains from the previous reports 31 . Surprisingly, most of the mutations were located in the C-terminus of NS1 ORF; 7 sense mutations were discovered (Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Mutations in the C-terminus of HBoV NS1 affect the function of NP1

Zhang

Zhu

Hao

et al. 2017

Sci Rep

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Human bocavirus 1 (HBoV1) is an autonomous parvovirus in the Bocaparvovirus genus. The multifunctional nuclear protein NP1 is involved in viral replication. In the present study, we found that the mutations in the C-terminus of NS1 affected NP1 function in viral replication. Knocking out NP1 expression in the recombinant infectious clone, on which the C-terminus of NS1 was mutated based on the clinical samples from nasopharyngeal aspirates, resulted in different degrees of decreased replication. The result suggested that NP1 facilitated the replication of viral genome but was not necessary, which is different from the minute virus of canines, where NP1 is essential for viral replication. Further studies showed that clinical mutations in the NP1 region did not affect viral genome replication, and UP1 promoted viral DNA replication. Our results suggested that the C-terminus of NS1 is important for viral replication and may be a target for regulating the replication of the viral genome.

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Correlation between nucleotide mutation and viral loads of human bocavirus 1 in hospitalized children with respiratory tract infection

Cited by 12 publications

References 25 publications

Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

Bocavirus Infection in Otherwise Healthy Children with Respiratory Disease

Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children

Mutations in the C-terminus of HBoV NS1 affect the function of NP1

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