Abstract
Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV) has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER), with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca2+ concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.
Highlights
Foot-and-mouth disease (FMD) is a highly contagious disease in animals and is on the Office International Des Epizooties (OIE) list of notifiable animal diseases[1]
Moffat et al studied the effects of foot-and-mouth disease virus (FMDV) 2BC and 3A on the early secretion pathway in infected cells and found that they block the delivery of proteins to the cell surface by interacting with the endoplasmic reticulum (ER) [17]
Our results are consistent with the findings reported by Moffat et al Membrane topology of the FMDV 2B protein in BHK-21cells
Summary
Foot-and-mouth disease (FMD) is a highly contagious disease in animals and is on the Office International Des Epizooties (OIE) list of notifiable animal diseases[1]. The 2B proteins of poliovirus and coxsackie virus contain two hydrophobic regions, and they can insert themselves into the membrane of the endoplasmic reticulum (ER) or the Golgi apparatus to modify cellular membrane permeability once they are expressed in host cells [10,11,12] These 2B proteins can disrupt the Ca2+ balance in host cells, inducing apoptosis [13, 14]. During expression in host cells, the 2B protein increases the membrane permeability of bacterial and mammalian cells and can increase the Ca2+ content in host cells, thereby inducing autophagy These results demonstrate that the FMDV 2B protein has the same properties as other viroporins, suggesting that the 2B proteins of picornaviruses may play the same role in virus infection
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