Flavivirus pre-membrane (prM) protein is important for proper folding and secretion of envelope (E) protein. However, other functions of prM protein in relation to virus life-cycle are poorly characterized. In this study, we aimed to elucidate if dengue virus (DENV) prM protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast two-hybrid library Our study identified claudin-1 as a novel interacting partner of DENV prM protein Virus production was significantly attenuated in claudin-1 knock-down cells We showed that claudin-1 expression is up-regulated at the early phase of infection to facilitate DENV entry and down-regulated at the late stage of infection probably to prevent super-infection. Our study also demonstrated that DENV C protein played an important role in down-regulating claudin-1 expression during DENV infection. (C) 2009 Elsevier Inc. All rights reserved