title: Respiratory syncytial virus human experimental infection model: provenance, production, and sequence of low-passaged memphis-37 challenge virus.
abstract: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children and is responsible for as many as 199,000 childhood deaths annually worldwide. To support the development of viral therapeutics and vaccines for RSV, a human adult experimental infection model has been established. In this report, we describe the provenance and sequence of RSV Memphis-37, the low-passage clinical isolate used for the model's reproducible, safe, experimental infections of healthy, adult volunteers. The predicted amino acid sequences for major proteins of Memphis-37 are compared to nine other RSV A and B amino acid sequences to examine sites of vaccine, therapeutic, and pathophysiologic interest. Human T- cell epitope sequences previously defined by in vitro studies were observed to be closely matched between Memphis-37 and the laboratory strain RSV A2. Memphis-37 sequences provide baseline data with which to assess: (i) virus heterogeneity that may be evident following virus infection/transmission, (ii) the efficacy of candidate RSV vaccines and therapeutics in the experimental infection model, and (iii) the potential emergence of escape mutants as a consequence of experimental drug treatments. Memphis-37 is a valuable tool for pre-clinical research, and to expedite the clinical development of vaccines, therapeutic immunomodulatory agents, and other antiviral drug strategies for the protection of vulnerable populations against RSV disease.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Children's Foundation Research Institute of Le Bonheur Children's Hospital, Memphis, Tennessee, United States of America.
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Children's Foundation Research Institute of Le Bonheur Children's Hospital, Memphis, Tennessee, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: DeVincenzo
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Bart G
authors.initials: BG
authors.lastname: Jones
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Rudraraju
authors.affiliation: Children's Foundation Research Institute of Le Bonheur Children's Hospital, Memphis, Tennessee, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Harrison
authors.affiliation: Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Meyers
authors.affiliation: Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States of America.
authors.forename: Jeff
authors.initials: J
authors.lastname: Cehelsky
authors.affiliation: Alnylam Pharmaceuticals, Cambridge, Massachusetts, United States of America.
authors.forename: Rene
authors.initials: R
authors.lastname: Alvarez
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D001988:Bronchiolitis / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D056945:Hep G2 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology / Q000627:therapeutic use; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013714:Tennessee; D016896:Treatment Outcome; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins