Topology and biological function of enterovirus non-structural protein 2B as a member of the viroporin family

Abstract

Viroporins are a group of transmembrane proteins with low molecular weight that are encoded by many animal viruses. Generally, viroporins are composed of 50-120 amino acid residues and possess a minimum of one hydrophobic region that interacts with the lipid bilayer and leads to dispersion. Viroporins are involved in destroying the morphology of host cells and disturbing their biological functions to complete the life cycle of the virus. The 2B proteins encoded by enteroviruses, which belong to the family Picornaviridae, can form transmembrane pores by oligomerization, increase the permeability of plasma membranes, disturb the homeostasis of calcium in cells, induce apoptosis, and cause autophagy; these abilities are shared among viroporins. The present paper introduces the structure and biological characteristics of various 2B proteins encoded by enteroviruses of the family Picornaviridae and may provide a novel idea for developing antiviral drugs.

Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis

“…Viroporins constitute a large class of multifunctional viral proteins with ion channel (IC) activity that are widely distributed among different viral families ( 9 ); highly pathogenic human viruses such as human immunodeficiency virus 1 (HIV-1), hepatitis C virus (HCV), influenza A virus (IAV), rotavirus (RV), enterovirus, and CoVs such as SARS-CoV and MERS-CoV encode them ( 10 – 16 ). Viroporins promote several steps of the virus replication cycle, including entry, genome replication, morphogenesis, and release from the infected cell ( 17 , 18 ).…”

Biological function of Foot-and-mouth disease virus non-structural proteins and non-coding elements

“…The transmembrane hydrophobic domains interact with the phospholipid bilayer to induce dispersion, increasing membrane permeability and promoting the release of viral particles. Thus, viroporins are crucial for viral pathogenicity [ 101 , 102 ].…”

Viral Membrane Channels: Role and Function in the Virus Life Cycle

“…In enteroviruses, the non-structural protein 2B forms pores in ER membrane, leading to leakage of calcium into the cytoplasm. Disruption of calcium homeostasis activates several host immune responses such as autophagy, which ultimately leads to cellular apoptosis (see review [ 41 ]). For example, in Coxsackievirus, 2B has been found to localize to the ER and plasma membrane at different stages of the infection.…”

“…A model has been proposed whereby 2B alters the permeability of the ER and plasma membrane to facilitate viral release by affecting the calcium content [ 39 ]. Subsequent viral release is most likely achieved through apoptosis induction via the calcium dependent mitochondrial pathway [ 40 , 41 ]. In Poliomaviruses such as SV40, proliferation occurs in the nuclei and release of infectious particles occurs following cells’ rupture [ 88 ].…”