Comprehensive Elucidation of the Role of L and 2A Security Proteins on Cell Death during EMCV Infection

• Published in: Viruses Vol. 16; no. 2; p. 280
• Main Authors: Ivin, Yury, Butusova, Anna, Gladneva, Ekaterina, Gmyl, Anatoly, Ishmukhametov, Aydar
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2024; MDPI
• Subjects: 2A protein; Apoptosis; Caspase; Caspases - genetics; Caspases - metabolism; Cell death; Cell lines; Deficient mutant; Development and progression; EMCV; Encephalomyocarditis virus - physiology; Genomes; HeLa Cells; Humans; Hypotheses; Infections; leader protein; Localization; Mutation; Phosphorylation; Physiological aspects; Picornavirus infections; Plasmids; Pyroptosis; RNA-protein interactions; security protein; Structure; viral infection; Viral infections; Viral proteins; Viral Proteins - genetics; Viral Proteins - metabolism; Virulence factors; Virus research; Viruses; Russia; 2A protein; security protein; viral infection; cell death; nuclear-cytoplasmic traffic; apoptosis; leader protein; EMCV
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v16020280

The EMCV L and 2A proteins are virulence factors that counteract host cell defense mechanisms. Both L and 2A exhibit antiapoptotic properties, but the available data were obtained in different cell lines and under incomparable conditions. This study is aimed at checking the role of these proteins in the choice of cell death type in three different cell lines using three mutants of EMCV lacking functional L, 2A, and both proteins together. We have found that both L and 2A are non-essential for viral replication in HeLa, BHK, and RD cell lines, as evidenced by the viability of the virus in the absence of both functional proteins. L-deficient infection led to the apoptotic death of HeLa and RD cells, and the necrotic death of BHK cells. 2A-deficient infection induced apoptosis in BHK and RD cells. Infection of HeLa cells with the 2A-deficient mutant was finalized with exclusive caspase-dependent death with membrane permeabilization, morphologically similar to pyroptosis. We also demonstrated that inactivation of both proteins, along with caspase inhibition, delayed cell death progression. The results obtained demonstrate that proteins L and 2A play a critical role in choosing the path of cell death during infection, but the result of their influence depends on the properties of the host cells.