Key result
The foot-and-mouth disease virus 2B protein functions as a viroporin by localizing to the endoplasmic reticulum, disrupting cell membrane integrity, increasing intracellular Ca2+, and inducing autophagy.
The FMDV 2B protein functions as a viroporin, disrupting cellular homeostasis and inducing autophagy, which provides insight into the infection mechanism of the foot-and-mouth disease virus.
May identify 2B as FMDV antiviral target; leaves open translation from cell models to livestock efficacy.
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 Ca(2+) 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.
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Ao et al. (2015) studied Foot-and-Mouth Disease Virus (FMDV) infection (in vitro). FMDV 2B protein expression vs. Empty vector or untreated cells was evaluated on Viroporin activity (membrane permeability, intracellular Ca2+ concentration, and autophagy induction). The foot-and-mouth disease virus 2B protein functions as a viroporin by localizing to the endoplasmic reticulum, disrupting cell membrane integrity, increasing intracellular Ca2+, and inducing autophagy.
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