Jitobaom Kunlakanya, Tongluan Natthida, Smith Duncan R
Institute of Molecular Biosciences Mahidol University, Salaya Campus, 25/25 Phuttamonthon Sai 4, Salaya, Nakhon Pathom 73170, Thailand.
Center for Emerging and Neglected Infectious Diseases, Mahidol University, Salaya Campus, 25/25 Phuttamonthon Sai 4, Salaya, Nakhon Pathom 73170, Thailand.
Sci Rep. 2016 Oct 25;6:35753. doi: 10.1038/srep35753.
During infection, dengue virus (DENV) proteins interact with host cellular constituents promoting the remodeling of the cell to facilitate virus production. While a number of interacting proteins have been identified for DENV non-structural proteins, far fewer interacting partners have been identified for the DENV structural proteins. One protein that has been identified as a DENV E protein interacting protein is the cellular chaperone GRP78. GRP78 has been shown to have a number of cellular interacting partners including the voltage-dependent anion channel (VDAC). In this study we confirmed the interactions between GRP78 and DENV E protein and between GRP78 and VDAC. VDAC was shown to be re-localized during DENV infection, with no change in levels of protein expression. VDAC is predominantly located on the outer membrane of mitochondria and our result is consistent with movement of the mitochondria towards the ER during DENV infection. Down regulation of VDAC through siRNA significantly reduced DENV protein expression, as well as the percentage infection and output virus titer. Our results suggest that VDAC plays an important role in DENV infection.
在感染过程中，登革病毒（DENV）蛋白与宿主细胞成分相互作用，促进细胞重塑以利于病毒产生。虽然已鉴定出许多与DENV非结构蛋白相互作用的蛋白，但与DENV结构蛋白相互作用的伴侣却少得多。一种已被鉴定为与DENV E蛋白相互作用的蛋白是细胞伴侣GRP78。GRP78已被证明有许多细胞相互作用伴侣，包括电压依赖性阴离子通道（VDAC）。在本研究中，我们证实了GRP78与DENV E蛋白之间以及GRP78与VDAC之间的相互作用。结果表明，在DENV感染期间VDAC会重新定位，而蛋白表达水平没有变化。VDAC主要位于线粒体外膜，我们的结果与DENV感染期间线粒体向内质网移动一致。通过小干扰RNA（siRNA）下调VDAC可显著降低DENV蛋白表达以及感染百分比和病毒产出滴度。我们的结果表明，VDAC在DENV感染中起重要作用。
