Interaction of dengue virus envelope protein with endoplasmic reticulum-resident chaperones facilitates dengue virus production.
Dengue virus infection is an important mosquito-borne disease and a public health problem worldwide. A better understanding of interactions between human cellular host and dengue virus proteins will provide insight into dengue virus replication and cellular pathogenesis. The glycosylated envelope protein of dengue virus, DENV E, is processed in the endoplasmic reticulum of host cells and therefore reliant on host processing functions. The complement of host ER functions involved and nature of the interactions with DENV E has not been thoroughly investigated. By employing a yeast two-hybrid assay, we found that domain III of DENV E interacts with human immunoglobulin heavy chain binding protein (BiP). The relevance of this interaction was demonstrated by co-immunoprecipitation and co-localization of BiP and DENV E in dengue virus-infected cells. Using the same approach, association of DENV E with two other chaperones, calnexin and calreticulin was also observed. Knocking-down expression of BiP, calnexin, or calreticulin by siRNA significantly decreased the production of infectious dengue virions. These results indicate that the interaction of these three chaperones with DENV E plays an important role in virion production, likely facilitating proper folding and assembly of dengue proteins.
Limjindaporn
Thawornchai
T
Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. limjindaporn@yahoo.com
Wongwiwat
Wiyada
W
Noisakran
Sansanee
S
Srisawat
Chatchawan
C
Netsawang
Janjuree
J
Puttikhunt
Chunya
C
Kasinrerk
Watchara
W
Avirutnan
Panisadee
P
Thiemmeca
Somchai
S
Sriburi
Rungtawan
R
Sittisombut
Nopporn
N
Malasit
Prida
P
Yenchitsomanus
Pa-thai
PT
D000818:Animals; D037281:Calnexin / Q000235:genetics / Q000378:metabolism; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D003715:Dengue / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication
D037282:Calreticulin; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; D037281:Calnexin