TRiC/CCT Complex, a Binding Partner of NS1 Protein, Supports the Replication of Zika Virus in Both Mammalians and Mosquitoes.

Yuchen Wang,Ryuta Uraki,Jesse Hwang,Erol Fikrig

doi:10.3390/v12050519

Yuchen Wang, Ryuta Uraki + Show 2 more

Open Access

https://doi.org/10.3390/v12050519

Copy DOI

Abstract

Mosquito-borne Zika virus (ZIKV) can cause congenital microcephaly and Guillain–Barré syndrome, among other symptoms. Specific treatments and vaccines for ZIKV are not currently available. To further understand the host factors that support ZIKV replication, we used mass spectrometry to characterize mammalian proteins that associate with the ZIKV NS1 protein and identified the TRiC/CCT complex as an interacting partner. Furthermore, the suppression of CCT2, one of the critical components of the TRiC/CCT complex, inhibited ZIKV replication in both mammalian cells and mosquitoes. These results highlight an important role for the TRiC/CCT complex in ZIKV infection, suggesting that the TRiC/CCT complex may be a promising therapeutic target.

Highlights

Zika virus (ZIKV) is a mosquito-borne enveloped, positive-strand RNA virus in the genusFlavivirus and the family Flaviviridae [1]
A previous study reported that an attenuated recombinant vesicular stomatitis virus-based vaccine expressing ZIKV precursor Membrane (prM)-E-NS1 induces ZIKV-specific antibody and T cell immune responses, providing protection against ZIKV challenge [9]
We found that the interaction between CCT2 and NS1 was ATP-dependent (Figure 3), suggesting ATP concentration may modulate the binding between ZIKV NS1 and TRiC/CCT complex, contributing to the ZIKV replication

Summary

Introduction

Zika virus (ZIKV) is a mosquito-borne enveloped, positive-strand RNA virus in the genusFlavivirus and the family Flaviviridae [1]. Zika virus (ZIKV) is a mosquito-borne enveloped, positive-strand RNA virus in the genus. The flavivirus RNA genome encodes three structural (capsid, premembrane, and envelope) and seven nonstructural genes (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5), with untranslated regions (UTR) flanking the 50 and 30 ends [6]. ZIKV nonstructural proteins play roles in viral replication and assembly [7]. A previous study reported that an attenuated recombinant vesicular stomatitis virus-based vaccine expressing ZIKV prM-E-NS1 induces ZIKV-specific antibody and T cell immune responses, providing protection against ZIKV challenge [9]. Monoclonal antibodies targeting NS1 protein can protect against disease and death in a murine model [10].

Methods

Results

Conclusion