Novel binding between pre-membrane protein and vacuolar ATPase is required for efficient dengue virus secretion.
Flavivirus pre-membrane (prM) protein is important for proper folding and secretion of envelope (E) protein. However, other non-structural functions of prM protein in the context of virus life-cycle are poorly known. In this study, we aimed to elucidate if dengue virus (DV) prM protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast-two-hybrid library. Our study identified vacuolar ATPase (V-ATPase) as a novel interacting partner of DV prM protein and aminoacid residues from 76 to 80 of prM protein are crucial to mediate V-ATPase binding. We showed that V-ATPase plays an important role in mediating low-pH dependent entry of DV. The biological significance of prM-V-ATPase interaction is also elucidated and we have shown that this association is critical to influence efficient virus egression. This study highlighted for the first time that flavivirus prM protein interacts with V-ATPase and V-ATPase mediates both entry and egression of DV.
Duan
Xiaoqun
X
Department of Pharmacology, Guilin Medical University, 109 Huancheng Road, Guilin, Guangxi 541004, PR China. robortduan@gmail.com
Lu
Xi
X
Li
Jun
J
Liu
Yongming
Y
D002460:Cell Line; D003716:Dengue Virus / Q000502:physiology*; D015723:Gene Library; D054884:Host-Pathogen Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000096:biosynthesis; D020798:Two-Hybrid System Techniques; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization; D017201:Virus Shedding
D012367:RNA, Viral; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus; D025262:Vacuolar Proton-Translocating ATPases