Human respiratory syncytial virus (HRSV), a member of the Pneumovirus genus within the Paramyxoviridae family, is recognized as the leading agent responsible for severe respiratory infections in the pediatric population (31, 34, 35) and a pathogen of considerable importance in vulnerable adults (23,24). The global respiratory syncytial virus (RSV) disease burden is estimated at 64 million cases and 160,000 deaths every year (70). This virus causes regular seasonal epidemics which take place during the winter months in temperate countries or during the rainy season in tropical areas (12). A peculiar aspect of HRSV is that the immune response produced by infection does not confer long-lasting protection, which is why reinfections are common throughout life (30).Neutralization tests performed with hyperimmune serum (16) and reactivity with specific monoclonal antibodies (4, 45) were used to classify HRSV isolates into two antigenic groups, A and B, which correlated with genetically distinct viruses (18). The main differences between these two groups are located in the major attachment G protein. This protein is a type II glycoprotein that shares neither sequence nor structural features with the attachment proteins (HN or H) of other paramyxoviruses (69), and it represents one of the targets of the immune response (27, 43). The full-length membranebound G protein (Gm) of 292 to 319 amino acids (depending on the viral strain) is also expressed in a secreted version (Gs) that lacks the transmembrane domain due to alternative initiation of translation at a second in-frame AUG codon in the G open reading frame (M48) (52). The G protein is the viral gene product with the highest degree of antigenic and genetic diversity among viral isolates (4,18,28,45). Most changes are concentrated in two hypervariable regions that flank a highly conserved central region of the G protein ectodomain, which includes a cluster of four cysteines and the putative receptor binding site (43). It has been suggested that antigenic differences within this protein could facilitate repeated HRSV infections (37,59). In addition, positive selection of amino acid changes was observed in the two hypervariable regions of the G protein ectodomain (7,43,71,73,74). One of the hypervariable regions, located in the C-terminal one-third of the G molecule, contains multiple epitopes recognized by monoclonal antibodies (43), suggesting that immune selection of new variants by antibodies may contribute to generation of HRSV diversity.Phylogenetic studies based on sequence analysis of the G protein have identified numerous genotypes in the antigenic groups A and B that show complex circulation patterns, since multiple genotypes of both antigenic groups may circulate within the same season and community, with one or two dominant genotypes being replaced in successive years (13,14,26,27,32,49,50). Each community shows a seasonal circulation
It is not clearly established if coinfections are more severe than single viral respiratory infections.The aim of the study was to study and to compare simple infections and viral coinfections of respiratory syncytial virus (RSV) in hospitalized children.From September 2005 to August 2013, a prospective study was conducted on children younger than 14 years of age, admitted with respiratory infection to the Pediatric Department of the Severo Ochoa Hospital, in Spain. Specimens of nasopharyngeal aspirate were taken for virological study by using polymerase chain reaction, and clinical data were recorded. Simple RSV infections were selected and compared with double infections of RSV with rhinovirus (RV) or with human bocavirus (HBoV).In this study, 2993 episodes corresponding to 2525 children were analyzed. At least 1 virus was detected in 77% (2312) of the episodes. Single infections (599 RSV, 513 RV, and 81 HBoV) were compared with 120 RSV-RV and 60 RSV-HBoV double infections. The RSV-RV coinfections had fever (63% vs 43%; P < 0.001) and hypoxia (70% vs 43%; P < 0.001) more often than RV infections. Hypoxia was similar between single or dual infections (71%). Bronchiolitis was more frequent in the RSV simple group (P < 0.001). Pediatric intensive care unit admission was more common in RSV simple or RSV-RV groups than in the RV monoinfection (P = 0.042).Hospitalization was longer for both RSV simple group and RSV-HBoV coinfection, lasting about 1 day (4.7 vs 3.8 days; P < 0.001) longer than in simple HBoV infections. There were no differences in PICU admission. RSV single group was of a younger age than the other groups.Coinfections between RSV-RV and RSV-HBoV are frequent. Overall viral coinfections do not present greater severity, but have mixed clinical features.
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