Identification of prohibitin as a Chikungunya virus receptor protein

Abstract

Chikungunya virus (CHIKV) has recently re-emerged causing millions of infections in countries around the Indian Ocean. While CHIKV has a broad host cell range and productively infects a number of different cell types, macrophages have been identified as a potential viral reservoir serving to increase the duration of symptoms. To date no CHIKV interacting protein has been characterized and this study sought to identify CHIKV binding proteins expressed on target cell membranes. Two-dimensional virus overlay identified prohibitin (PHB) as a microglial cell expressed CHIKV binding protein. Co-localization, co-immunoprecipitation as well as antibody and siRNA mediated infection inhibition studies all confirmed a role for PHB in mediating internalization of CHIKV into microglial cells. PHB is the first identified CHIKV receptor protein, and this study is evidence that PHB may play a role in the internalization of multiple viruses.

Chikungunya and Its Interaction With the Host Cell

“…These later authors also have found evidence that multiple pathways maybe employed by CHIKV to enter into cells, as already proposed with dengue virus (DENV) [67,68]. Another possible explanation could be that there are cell type specific differences implied in the entry mechanism [62].…”

“…The E1 glycoprotein is a class II fusion protein that mediates fusion of the viral and host cell membranes during virus entry, while the E2 glycoprotein is a 50-kDa type I trans-membrane glycoprotein that is responsible for receptor binding to host cells [61,62]. Viral replication is initiated by attachment of viral envelope to host cell receptors [63], followed by low pH-mediated membrane fusion and delivery of the viral nucleocapsid into the cytoplasm (Fig.…”

“…However, some authors have identified prohibitin (PHB) as CHIKV-binding protein expressed by microglial cells [62], while other authors suggest that the heat shock proteins (HSPs) may play a crucial role in the virus entry. More in detail, Paingankar and colleagues (2014) have identified HSP70 as virus-binding protein in HEK-293T cells and Vero-E6, also assessing that STAT-2 could be involved in this mechanism, especially in Vero-E6 cells.…”

Recent progress on chikungunya virus research

“…CHIKV replication in these cells induces cytopathic effects which can be used to test its virulence and dissect the detailed steps of virus life cycle. The CHIKV specific entry receptor is yet to be defined, but several putative receptors facilitate virus infection, including Glycosaminoglycans (GAGs), Prohibitin (PHB), Dendritic Cell-Specific Intercellular adhesion molecule (ICAM)-3-Grabbing Non-integrin (DC-SIGN, CD209) and Liver lymph node-specific ICAM-3-grabbing integrin (L-SIGN) (Klimstra et al, 2003;Wintachai et al, 2012;Weber et al, 2017).…”

Chikungunya

“…1). 31 Two precursors of non-structural proteins are translated from the viral mRNA,and cleavage of these precursors generates nsP1-nsP4. 32 These proteins assemble to form the viral replication com-plex, which synthesizes a full-length negative-strand RNAintermediate.…”