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Cellular Factors Implicated in Filovirus Entry

DOI: 10.1155/2013/487585

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Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. 1. Introduction The Filoviridae family comprises of three genera: Ebolavirus, Marburgvirus, and Cuevavirus (tentative). These enveloped viruses are nonsegmented with negative-sense RNA and produce filamentous virions, which are pleomorphic in shape [1]. Ebolavirus has five known species: Zaire (EBOV), Sudan (SUDV), Reston (RESTV), Tai Forest (TAFV), and Bundibugyo (BDBV) while Marburgvirus has only one species: Marburg virus (MARV) [2–9]. EBOV and MARV and are known to be serologically, biochemically, and genetically distinct [10, 11]. The filoviral genome encodes seven structural proteins: envelope glycoprotein (GP), major matrix protein (VP40), nucleoprotein (NP), polymerase cofactor (VP35), replication/transcription protein (VP30), minor matrix protein (VP24), and RNA dependent DNA polymerase (L). In addition to this, EBOV also expresses a small, secreted, nonstructural glycoprotein (sGP) (see [12] for a comprehensive review). Filoviruses are transmitted through contact with infected blood or body fluids [13] and can infect many cell types across different host species with lymphocytes being the notable exception [14, 15]. Although filoviruses are known to be pantropic, their preferred target cells

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