title: A conserved region in the prM protein is a critical determinant in the assembly of flavivirus particles.
abstract: Flaviviruses are assembled to bud into the lumen of the endoplasmic reticulum (ER) and are secreted through the vesicle transport pathway, but the details of the molecular mechanism of virion assembly remain largely unknown. In this study, a highly conserved region in the prM protein was identified among flaviviruses. In the subviral particle (SP) system of tick-borne encephalitis virus (TBEV) and Japanese encephalitis virus, secretion of SPs was impaired by a mutation in the conserved region in the prM protein. Viral proteins were sparse in the Golgi complex and accumulated in the ER. Ultrastructural analysis revealed that long filamentous structures, rather than spherical SPs, were observed in the lumen of the ER as a result of the mutation. The production of infectious virions derived from infectious cDNA of TBEV was also reduced by mutations in the conserved region. Molecular modelling analysis suggested that the conserved region is important for the association of prM-envelope protein heterodimers in the formation of a spike of immature virion. These results are the first demonstration that the conserved region in the prM protein is a molecular determinant for the flavivirus assembly process.
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoshii
authors.affiliation: Department of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.affiliation: Laboratory of Anatomy, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ichii
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Yokozawa
authors.affiliation: Department of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Kimihito
authors.initials: K
authors.lastname: Ito
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kariwa
authors.affiliation: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Takashima
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D004664:Encephalitis Virus, Japanese / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004669:Encephalitis Viruses, Tick-Borne / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004675:Encephalitis, Tick-Borne / Q000821:virology*; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D019065:Virus Assembly
chemical_list: D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus