Abstract

In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV) and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009–2010, 2010–2011, 2011–2012, 2012–2013 and 2013–2014). The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4%) carried RSV-A and 34 (20.6%) RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010–2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001) and required hospitalisation (p = 0.007) more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.

Highlights

  • Human respiratory syncytial virus (RSV) is the second most frequent cause of respiratory infections, and the main cause of severe cases of bronchiolitis and pneumonia in infants and young children [1].Classified in the Pneumovirus genus of the family Paramyxoviridae, it is an enveloped virus with a negative-sense single-strained RNA genome that encodes for 11 proteins [2], including two surface glycoproteins that are antigenically significant because they induce neutralising antibody responses: fusion protein (F protein) and attachment glycoprotein (G protein)

  • In order to evaluate the circulation of the different RSV types and genotypes, and the possible relationships between their genetic characteristics and the severity of RSV infection, we studied all of the nasopharyngeal samples exclusively positive for RSV collected from children aged

  • The findings of this study show that RSV has complex circulation patterns that are characterised by the periodic replacement of the predominant genotypes with new ones during successive epidemic seasons

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Summary

Introduction

Human respiratory syncytial virus (RSV) is the second most frequent cause of respiratory infections, and the main cause of severe cases of bronchiolitis and pneumonia in infants and young children [1].Classified in the Pneumovirus genus of the family Paramyxoviridae, it is an enveloped virus with a negative-sense single-strained RNA genome that encodes for 11 proteins [2], including two surface glycoproteins that are antigenically significant because they induce neutralising antibody responses: fusion protein (F protein) and attachment glycoprotein (G protein). On the basis of their reactions with monoclonal antibodies, the viral strains have been separated into two major serotypes (RSV-A and RSV-B), and nucleotide sequence analysis has led to the identification of 11 RSV-A (GA1-GA7, SAA1, NA1-NA2, and ON1) [2,3,4] and 23 RSV-B genotypes, (GB1-GB4, SAB1-SAB3, SAB4, URU1, URU2, BA1-BA12 and THB) [5,6,7,8,9,10,11,12,13]. Multiple genotypes can co-circulate during successive epidemic seasons, but a new genotype (or one spreading from another country) may replace previously dominant strains [5,14,15]. The rapid spread of a novel RSV-A genotype (A/ON1, replacing the ancestor A/NA1) has recently been documented in a number of countries [13,16,17,18,19,20,21]. RSV molecular epidemiological surveillance is essential for detecting the emergence of new viral strains, identifying or predicting their clinical relevance, selecting candidate strains for vaccine development, and preparing public health intervention strategies based on phylogeographic analysis

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