Cellular Attachment and Entry Factors for Chikungunya Virus.

Barbara S Schnierle

doi:10.3390/v11111078

Abstract

Chikungunya virus (CHIKV) is clinically the most relevant member of the Alphavirus genus. Like alphaviruses in general, CHIKV has the capacity to infect a large variety of cells, tissues, and species. This broad host tropism of CHIKV indicates that the virus uses a ubiquitously expressed receptor to infect cells. This review summarizes the current knowledge available on cellular CHIKV receptors and the attachment factors used by CHIKV.

Highlights

Like alphaviruses in general, Chikungunya virus (CHIKV) has the capacity to infect a large variety of cells, tissues, and species
The E2 protein is thought to be responsible for receptor binding, because it is the main target of neutralizing antibodies
The E2 protein belongs to the immunoglobulin superfamily and has three immunoglobulin domains—domain A is in the center, domain B is at the end of the spike, and domain C is membrane proximal and hidden from the virus surface

Summary

Virus Cell Entry

Infection of a target cell starts with the attachment of the virus to the cell surface. They demonstrated this using knockdown of Eps and clathrin heavy chain, a major scaffold protein of the clathrin coat [13] This suggests that several pathways are used by CHIKV to facilitate its entry into target cells. After entering the endosomal compartment, fusion of CHIKV with the host cell membrane depends on a low pH environment as lysomotropic agents, like chloroquine or bafilomycin A1, considerably inhibit CHIKV infection [13], [14]. Macropinosomes are large, uncoated vesicles involved in unspecific uptake of extracellular material Their formation is actin-dependent and is initiated by the stimulation of growth factor receptors by the virus. This results in signal transduction in the host cells and actin filament polarization, which pushes the membrane forward to form ruffles. Some of these ruffles fold inwards and fuse with the cell membrane forming macropinosomes that take up bound viruses [16] (Figure 2)

Cellular Proteins Interacting with CHIKV

Conclusions