Viroporins are small, usually hydrophobic multifunctional viral proteins that modify cellular membranes.
They facilitate virus release from infected cells by assembling into oligomeric ion channels or pores in the host cell’s membrane, rendering it more permeable and thus facilitating the exit of virions from the cell.
The most well-established function of viroporins is the permeabilization of the cell membrane to ions and small solutes.
Viroporins also have additional effects on cellular metabolism and homeostasis mediated by protein-protein interactions with host cell proteins.
Viroporins enhance viral growth rates, but are not essential for viral replication.
Most viroporins are not essential, but their absence significantly reduces the efficiency of viral propagation.
Associated with a a variety of viral genomes, and are particularly common in RNA viruses.
Many viruses that cause human disease express viroporins: hepatitis C virus, HIV-1, influenza A virus, poliovirus, respiratory syncytial virus, and Coronavirus.
Viroporins are usually small, under 100 or 120 amino acid residues.
Viroporins contain at least one region capable of folding into an amphipathic transmembrane helix, and
stretches of basic amino acids, or stretches of aromatic amino acids thought to reside in the interfacial region of the membrane.
These oligomer proteins, most often tetramers, form ion channels or pores that permit diffusion of ions across the cell membrane.
Viroporins vary in their ability to effect the architecture of cell membrane’s pores, in selectivity, in the ability to incorporate lipids and to extend beyond the cellular membrane, and in their array of other roles.
Viroporins are observed to localize to the Golgi apparatus and other cytoplasmic structures during viral infection.
Viroporins activate the NLRP3 inflammasome by inducing different ionic fluxes.
A proposed classification of viroporins into four classes based on their topology and orientation in the membrane.
There are marked variation in the consequences of viroporin depletion: while hepatitis C virus is incapable of propagation without its p7 protein viroporin
influenza A virus and HIV-1 see decreases in in vitro viral titer of 10- to 100-fold in the absence of their respective viroporins, but remain capable of propagation.
Pores formed by viroporins are nonselective or only weakly selective for particular ions or small molecules.
Some, however, do show strong selectivity.
In enveloped viruses, viroporins are not highly concentrated in the viral envelope, but nevertheless their presence may promote viral entry into the cell.
Viroporins in the membranes of organelles such as the Golgi apparatus can influence the internal environments, and modulate protein trafficking of viral proteins or protect the proteins from the low pH in these cellular compartments.
In non-enveloped viruses, the membrane permeability changes may be sufficient to induce cell lysis, permitting the new virions to exit the cell.
In enveloped viruses, viroporins’ depolarization effect promote viral budding.
Diminishing the ion channel or pore function of viroporins, by mutations that block conductance or through channel-blocking drugs, reduces or eliminates viral propagation.
Most viruses encoding viroporins can replicate their genomes in the absence of the viroporin, even if they are impaired in propagation.
Rotaviruses and picornaviruses, use viroporins to facilitate the formation of viroplasm, or the specialized intracellular compartments from the membrane of the endoplasmic reticulum in which genome replication occurs.
Some viroporins exert their effects through protein-protein interactions.
Viroporins are considered virulence factors.
In some cases the membrane permeabilization effects of viroporins activate the inflammasome, a protein complex associated with activation of innate immunity which, when overactive, can cause disease symptoms.
The human papillomavirus 16 E5 protein, is an oncogenic viroporin.
Amantadine, used against influenza A is an example of a viroporin-targeting drug:
Cochrane review did not find benefit for its use in children or elderly people.
Viroporins arebfound in a large number of viruses with distinct genomic organizations and replication mechanisms.