Evidence of recombination and genetic diversity in human rhinoviruses in children with acute respiratory infection.
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.


RESULTS
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.


CONCLUSIONS
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.
Huang
Ting
T
Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai Institute of Biological Sciences, Unit of Emerging Viruses, Shanghai, PR China.
Wang
Wei
W
Bessaud
Mael
M
Ren
Peijun
P
Sheng
Jun
J
Yan
Huajie
H
Zhang
Jing
J
Lin
Xin
X
Wang
Yongjin
Y
Delpeyroux
Francis
F
Deubel
Vincent
V
D020121:5' Untranslated Regions; D000208:Acute Disease; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012141:Respiratory Tract Infections / Q000821:virology*; D012229:Rhinovirus / Q000145:classification / Q000235:genetics*
D020121:5' Untranslated Regions; D017931:DNA Primers