The CD147 Protein Complex Is Involved in Entry of Chikungunya Virus and Related Alphaviruses in Human Cells.

Lien De Caluwé,Kevin K Ariën,Maarten Dhaenens,Koen Bartholomeeusen,Dieter Deforce,Katleen Vereecken,Sandra Coppens,Simon Daled,Xaveer Van Ostade

doi:10.3389/fmicb.2021.615165

Abstract

Chikungunya virus (CHIKV) is an arbovirus with a global spread and significant public health impact. It is a positive stranded RNA alphavirus belonging to the Togaviridae family. However, many questions about the replication cycle of CHIKV remain unanswered. The entry process of CHIKV is not completely understood nor are the associated virus-receptor interactions fully identified. Here, we designed an affinity purification mass spectrometry coupled approach that allowed the identification of factors that facilitate entry of CHIKV in human cells. The identified entry factors were further validated using CRISPR/Cas9. In HEK293T cells we identified the CD147 protein complex as an entry factor for CHIKV. We further showed the involvement of the CD147 protein complex in the replication cycle of related alphaviruses. Interestingly, CD147 contains similar protein domains as the previously identified alphavirus entry factor MXRA8.

Highlights

Chikungunya virus (CHIKV), an alphavirus from the Togaviridae family, is mainly transmitted by the bite of infected female Aedes mosquitos, primarily Aedes aegypti and Aedes albopictus (Mascarenhas et al, 2018)
We found that the E2 N-terminal tagged (E2-Nt) tagged construct had an equivalent infectivity compared to the WT CHIKV envelope
To further generalize our observation, we investigated the role of the CD147 protein complex in the entry of Asian, West African (WA) and Indian Ocean lineage (IOL) CHIKV as well as in the entry of the related alphaviruses o’nyong’nyong virus (ONNV), Mayaro virus (MAYV), Ross River virus (RRV), Sindbis virus (SINV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV)

Summary

Introduction

Chikungunya virus (CHIKV), an alphavirus from the Togaviridae family, is mainly transmitted by the bite of infected female Aedes mosquitos, primarily Aedes aegypti and Aedes albopictus (Mascarenhas et al, 2018). It is a spherical, enveloped, positive stranded RNA virus and is about 60–70 nm in diameter (Solignat et al, 2009). West African (WA), Asian, East/Central/South African (ECSA) and Indian Ocean lineage (IOL). The latter emerged from the ECSA lineage in 2005 (Weaver and Forrester, 2015). Neither specific antiviral treatment nor a licensed vaccine is available and treatment of CD147 in Alphavirus Entry

Methods

Results

Conclusion