Deep sequencing of RSV from an adult challenge study and from naturally infected infants reveals heterogeneous diversification dynamics

• Published in: Virology (New York, N.Y.) Vol. 510; pp. 289 - 296
• Main Authors: Lau, Jessica W., Kim, Young-In, Murphy, Ryan, Newman, Ruchi, Yang, Xiao, Zody, Michael, DeVincenzo, John, Grad, Yonatan H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017
• Subjects: acute course; Adult; adults; Deep sequencing; epitopes; Epitopes, B-Lymphocyte - genetics; Epitopes, T-Lymphocyte - genetics; Evolution, Molecular; genes; Genetic Variation; Genomics; High-Throughput Nucleotide Sequencing; hosts; Human orthopneumovirus; Humans; immune response; Infant; infant diseases; infants; infectious diseases; inoculum; Mutation; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus, Human - classification; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - isolation & purification; respiratory tract diseases; RSV; T-lymphocytes; Viral evolution; viral nonstructural proteins; Viral Proteins - genetics; Within-host diversity; Deep sequencing; Within-host diversity; RSV; Viral evolution; Genomics
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2017.07.017

As RNA virus mutation occurs during replication within host cells, we hypothesized that viral evolution during acute infections in healthy hosts reflects host immune pressure. We therefore investigated the within-host diversification of human respiratory syncytial virus (RSV), a highly prevalent cause of acute respiratory infections. We evaluated healthy adults experimentally infected with an identical inoculum and infants hospitalized with naturally acquired infections. In aggregate, viral diversification in adults peaked at day 3, with overrepresentation of diversity in the matrix protein 2 (M2) and non-structural protein 2 (NS2) genes. In one subject, delayed viral clearance was accompanied by a late peak of diversity at day 10 in known and predicted B and T cell epitopes. In contrast, infant infections showed much less viral diversity. Our findings suggest multiple overlapping mechanisms for early control of acute viral infections, which may differ between age groups and host immune responses. •Most adults cleared RSV quickly, with diversity overrepresented in NS2 and M2.•Delayed viral clearance was associated with diversity in B and T cell epitopes.•Infant infections showed much less diversity.•Our data suggest overlapping mechanisms for early control of acute viral infections.•These may differ between age groups and host immune responses.