Hsp90 interacts with multiple dengue virus 2 proteins

Kanjana Srisutthisamphan,Krit Jirakanwisal,Suwipa Ramphan,Atichat Kuadkitkan,Duncan R Smith,Natthida Tongluan

doi:10.1038/s41598-018-22639-5

Kanjana Srisutthisamphan, Krit Jirakanwisal + Show 4 more

Open Access

https://doi.org/10.1038/s41598-018-22639-5

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Journal: Scientific Reports	Publication Date: Mar 9, 2018
Citations: 24	License type: open-access

Affiliation: Mahidol University

Abstract

Infections with the mosquito-borne dengue virus (DENV) remain a significant public health challenge. In the absence of a commercial therapeutic to treat DENV infection, a greater understanding of the processes of cellular replication is required. The abundant cellular chaperone protein heat shock protein 90 (Hsp90) has been shown to play a proviral role in the replication cycle of several viruses, predominantly through the stabilization of specific viral proteins. To investigate any potential role of Hsp90 in DENV infection the interaction between Hsp90 and DENV proteins was determined through co-immunoprecipitation experiments. Six DENV proteins namely envelope (E) and nonstructural (NS) proteins NS1, NS2B, NS3, NS4B and NS5 were shown to interact with Hsp90, and four of these proteins (E, NS1, NS3 and NS5) were shown to colocalize to a variable extent with Hsp90. Despite the extensive interactions between Hsp90 and DENV proteins, inhibition of the activity of Hsp90 had a relatively minor effect on DENV replication, with inhibition of Hsp90 resulting in a decrease of cellular E protein (but not nonstructural proteins) coupled with an increase of E protein in the medium and an increased virus titer. Collectively these results indicate that Hsp90 has a slight anti-viral effect in DENV infection.

Highlights

Dengue virus (DENV) is an arthropod-borne virus that can cause a febrile illness in humans that is sometimes associated with severe bleeding and hypovolemic shock[1]
For example while GRP78 has been identified as a receptor protein for DENV10, cellular interactions between dengue virus (DENV) proteins and GRP78 have been reported[11,12]
To determine the intracellular levels of Hsp[90] during infection, HEK293T cells were infected with Dengue virus serotype 2 (DENV 2) at MOI 1

Summary

Introduction

Dengue virus (DENV) is an arthropod-borne virus that can cause a febrile illness (dengue fever, DF) in humans that is sometimes associated with severe bleeding (dengue hemorrhagic fever, DHF) and hypovolemic shock (dengue shock syndrome, DSS)[1]. Cellular infection with DENV starts with the attachment of the virus to host cell surface proteins and a number of putative receptors have been identified (reviewed in[6,7]). Previous reports have shown that Hsp[90] has a role in the replication of a number of viruses, including mumps virus[24], hepatitis C virus[25], rabies virus[26] and chikungunya virus[27,28] In all of these studies the action of Hsp[90] promotes virus replication, often through interacting with, and stabilizing specific viral proteins. This study sought to systematically survey all ten DENV proteins to determine if any proteins besides DENV E protein interacted with Hsp[90], as well as more broadly investigate the role of Hsp[90] in DENV replication

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