Abstract

Dengue virus (DENV) remains a significant public health problem in many tropical and sub-tropical countries worldwide. The DENV envelope (E) protein is the major antigenic determinant and the protein that mediates receptor binding and endosomal fusion. In contrast to some other DENV proteins, relatively few cellular interacting proteins have been identified. To address this issue a co-immuoprecipitation strategy was employed. The predominant co-immunoprecipitating proteins identified were actin and actin related proteins, however the results suggested that actin was the only bona fide interacting partner. Actin was shown to interact with the E protein of DENV 2 and 4, and the interaction between actin and DENV E protein was shown to occur in a truncated DENV consisting of only domains I and II. Actin was shown to decrease during infection, but this was not associated with a decrease in gene transcription. Actin-related proteins also showed a decrease in expression during infection that was not transcriptionally regulated. Cytoskeletal reorganization was not observed during infection, suggesting that the interaction between actin and E protein has a cell type specific component.

Highlights

  • Dengue virus (DENV) is the most common cause of arthropod-borne viral infection in tropical and subtropical countries [1]

  • HEK293T/17 was chosen as a model cell line as our previous work has shown this cell lines is both infectable with DENV [25] and transfectable with plasmid constructs [26], as a cell line derived from human embryonic kidney [27] it is of uncertain clinical significance in the pathophysiology of dengue infection

  • Evidence suggests that the DENV proteins are multifunctional in that they target specific host cell processes in addition to their functions as structural proteins that will form the new virus progeny or non-structural proteins directly involved in viral replication

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Summary

Introduction

Dengue virus (DENV) is the most common cause of arthropod-borne viral infection in tropical and subtropical countries [1]. DENV is an enveloped positive sense single stranded RNA virus belonging to the family Flaviviridae, genus Flavivirus. There are four antigenically distinct DENVs each of which can cause disease in humans ranging from a self-limited febrile illness known as dengue fever (DF) to more severe hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [3]. The DENV virion is composed of three structural proteins (capsid (C), membrane (M) and envelope protein (E)) and an approximately 11 kb RNA genome which encodes the three structural proteins (C, M, and E protein) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [4].

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