title: Evidence that a polyhexameric genome length is preferred, but not strictly required, for efficient mumps virus replication.
abstract: Mumps virus (MuV) is postulated to adhere to the "rule of six" for efficient replication. To examine the requirement for MuV, minigenomes of nonpolyhexameric length (6n-1 and 6n+1) were analyzed. Expression of the reporter gene CAT was significantly reduced with minigenomes of nonpolyhexameric length compared to the wild type 6n genome, and reduction was more pronounced for the 6n-1 than for the 6n+1 minigenome. That 6n-1 genomes are impacted by nonconformance with the rule of six to a greater degree as compared to 6n+1 genomes was also suggested with MuV derived from cDNA coding for 6n+1 or 6n-1 genomes. While viruses recovered from 6n+1 cDNAs maintained a nonpolyhexameric genome length over multiple replication cycles, viruses rescued from the 6n-1 cDNAs acquired length correcting mutations rapidly following rescue. Our data indicate that polyhexameric genomes are the preferred template for the MuV RNA polymerase, but that this requirement is not absolute.
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America. Electronic address: christian.sauder@fda.hhs.gov.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Sauder
authors.affiliation: Office of Biostatistics and Epidemiology, CBER, FDA, Silver Spring, MD, United States of America.
authors.forename: Vahan
authors.initials: V
authors.lastname: Simonyan
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ngo
authors.affiliation: Office of Biostatistics and Epidemiology, CBER, FDA, Silver Spring, MD, United States of America.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Karagiannis
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Facility for Biotechnology Resources, CBER, FDA, Silver Spring, MD, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Facility for Biotechnology Resources, CBER, FDA, Silver Spring, MD, United States of America.
authors.forename: Wells W
authors.initials: WW
authors.lastname: Wu
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America.
authors.forename: Tahir
authors.initials: T
authors.lastname: Malik
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D018076:DNA, Complementary; D004279:DNA, Viral; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D059646:Genome Size; D016679:Genome, Viral; D009109:Mumps virus / Q000235:genetics / Q000502:physiology*; D014709:Vero Cells; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D004279:DNA, Viral; D014764:Viral Proteins; C062210:bacteriophage T7 RNA polymerase; D012321:DNA-Directed RNA Polymerases
keywords: CAT; Full-length cDNA; High throughput sequencing; Minigenome; Mumps virus; Nonpolyhexameric genome; Paramyxovirinae; Replication; Rule of six; Virus rescue