What is the clinical evidence from this study?

Study design: Observational. Population: Acute respiratory infection (n=827). Intervention: Human rhinovirus infection. Primary outcome: Prevalence and genetic diversity of HRV strains.

July 24, 2009PLoS ONE106 citationsOpen Access

Evidence of Recombination and Genetic Diversity in Human Rhinoviruses in Children with Acute Respiratory Infection

THTing Huang WWWei Wang MBMaël Bessaud

Key Result

Among 64 HRV-infected children with acute respiratory infection, 51.5% of strains belonged to the novel HRV-C species, which exhibited high genetic diversity and evidence of recombination with HRV-A strains.

Study Design

Type

Observational (n=827)

Multicenter

Structured PICO

Population

827 children aged 5 months to 14 years with acute respiratory infection visiting a district hospital in Shanghai over a 2-year period, of which 64 were diagnosed with HRV infection.

Outcome

Identification, typing, and genetic diversity of HRV strainssurrogate

This study demonstrates a high genetic diversity of human rhinoviruses in children with acute respiratory infections, highlighting the predominance and recombination events of the newly identified HRV-C species.

Limitations

None of the patients in the study were hospitalized, making comparison with hospitalized children difficult.
More studies are needed on large numbers of samples from severe and mild diseases to identify the role of HRV sequence diversity in disease severity.
Differences in the size and location of the amplified regions in previous studies made comparative genetic analysis difficult.

Abstract

BACKGROUND: Human rhinoviruses (HRVs) are a highly prevalent cause of acute respiratory infection in children. They are classified into at least three species, HRV-A, HRV-B and HRV-C, which are characterized by sequencing the 5' untranslated region (UTR) or the VP4/VP2 region of the genome. Given the increased interest for novel HRV strain identification and their worldwide distribution, we have carried out clinical and molecular diagnosis of HRV strains in a 2-year study of children with acute respiratory infection visiting one district hospital in Shanghai. METHODOLOGY/FINDINGS: We cloned and sequenced a 924-nt fragment that covered part of the 5'UTR and the VP4/VP2 capsid genes. Sixty-four HRV-infected outpatients were diagnosed amongst 827 children with acute low respiratory tract infection. Two samples were co-infected with HRV-A and HRV-B or HRV-C. By comparative analysis of the VP4/VP2 sequences of the 66 HRVs, we showed a high diversity of strains in HRV-A and HRV-B species, and a prevalence of 51.5% of strains that belonged to the recently identified HRV-C species. When analyzing a fragment of the 5' UTR, we characterized at least two subspecies of HRV-C: HRV-Cc, which clustered differently from HRV-A and HRV-B, and HRV-Ca, which resulted from previous recombination in this region with sequences related to HRV-A. The full-length sequence of one strain of each HRV-Ca and HRV-Cc subspecies was obtained for comparative analysis. We confirmed the close relationship of their structural proteins but showed apparent additional recombination events in the 2A gene and 3'UTR of the HRV-Ca strain. Double or triple infections with HRV-C and respiratory syncytial virus and/or bocavirus were diagnosed in 33.3% of the HRV-infected patients, but no correlation with severity of clinical outcome was observed. CONCLUSION: Our study showed a high diversity of HRV strains that cause bronchitis and pneumonia in children. A predominance of HRV-C over HRV-A and HRV-B was observed, and two subspecies of HRV-C were identified, the diversity of which seemed to be related to recombination with former HRV-A strains. None of the HRV-C strains appeared to have a higher clinical impact than HRV-A or HRV-B on respiratory compromise.

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