title: Polypyrimidine tract-binding protein influences negative strand RNA synthesis of dengue virus.
abstract: Flavivirus non-structural protein 4A (NS4A) induces membrane rearrangements to form viral replication complex and functions as interferon antagonist. However, other non-structural roles of NS4A protein in relation to virus life-cycle are poorly defined. This study elucidated if dengue virus (DENV) NS4A protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast-two-hybrid library. Our study identified polypyrimidine tract-binding protein (PTB) as a novel interacting partner of DENV NS4A protein. We reported for the first time that PTB influenced DENV production. Gene-silencing studies showed that PTB did not have an effect on DENV entry and DENV RNA translation. Further functional studies revealed that PTB influenced DENV production by modulating negative strand RNA synthesis. This is the first study that enlightens the interaction of DENV NS4A protein with PTB, in addition to demonstrating the novel role of PTB in relation to mosquito-borne flavivirus life-cycle.
authors.affiliation: Institute of Biotechnology, Guilin Medical University, Guilin, Guangxi, PR China.
authors.forename: Linbin
authors.initials: L
authors.lastname: Jiang
authors.forename: Huiling
authors.initials: H
authors.lastname: Yao
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Duan
authors.forename: Xi
authors.initials: X
authors.lastname: Lu
authors.forename: Yongming
authors.initials: Y
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D003715:Dengue / Q000378:metabolism / Q000821:virology*; D003716:Dengue Virus / Q000378:metabolism / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis* / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C080106:NS4A protein, flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D038941:Polypyrimidine Tract-Binding Protein