Molecular Characterization of Respiratory Syncytial Virus in Children With Repeated Infections With Subgroup B in the Philippines

Abstract

BackgroundHuman respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes.MethodsWe conducted a cohort study of children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between initial and subsequent RSV infections.ResultsWe examined 1802 children from May 2014 to January 2016 and collected 3471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein.ConclusionsAmino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

Age‐specific incidence rates and risk factors for respiratory syncytial virus‐associated lower respiratory tract illness in cohort children under 5 years old in the Philippines

“…Nasopharyngeal swabs were collected from RTI for RSV testing as described previously, 27 including real-time polymerase chain reaction (PCR) to screen for RSV, 28,29 conventional PCR for subgrouping and sequencing of the second variable region of the G gene (RSV-A: 342 bp and RSV-B: 330 bp). 30,31 Testing for RSV and other viruses, including rhinovirus, enterovirus, human metapneumovirus, human adenovirus, parainfluenza virus and influenza virus, was conducted using primers described in Supporting Information Table S2.…”

“…Fast breathing is one of the criteria for LRTI, and the cut-off points differ by age (50 breaths/min in children aged 2-11 months and 40 breaths/min in children aged 12-59 months 25 [11,42] 19 [11,30] 16 [10,23] 12 [6,17] 18 [10,27] 15 [9,22] 19 [10,31] Age in months, n (%) 2-5…”

“…. Caibiran had a larger epidemic of RSV, and particularly RSV-B, in 2015 27. Although the reasons for such differences are unknown, epidemiological patterns of RSV epidemics including their size can vary among different locations and also between epidemics even in the same location.…”

Complete Genome Sequences of 12 Human Respiratory Syncytial Virus ( Human Orthopneumovirus ) Strains Detected in Children with Repeated Subgroup B Infections in the Philippines

“…Previous reports on repeated infections with homologous RSV subgroups analyzed only partial gene sequences ( 4 – 7 ). Using Sanger sequencing, we previously identified five amino acid substitutions in the G and F genes that may be associated with repeated infections ( 8 ). However, mutations in other genes may also be involved in repeated infections.…”

“…This prospective cohort study was conducted on children with acute respiratory infections in the Philippines during 2014 to 2017. Previously, repeated RSV-B infections were detected in four children ( 8 ). Further analysis identified two additional children with these infections.…”