Human hepatitis A virus 3C protease exerts a cytostatic effect on Saccharomyces cerevisiae and affects the vacuolar compartment

Shubin, Andrey V.; Komissarov, Alexey A.; Karaseva, Maria A.; Padman, Benjamin Scott; Kostrov, Sergey V.; Demidyuk, Ilya V.

doi:10.2478/s11756-020-00569-w

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…Similar results were also observed upon expression of Hepatitis A virus 3C protease in S. cerevisiae. The authors report distortion and fragmentation of vacuole (Shubin et al 2021).…”

Section: Rna Virusesmentioning

confidence: 97%

Contribution of yeast models to virus research

Glingston

Yadav

Rajpoot

et al. 2021

Appl Microbiol Biotechnol

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Time and again, yeast has proven to be a vital model system to understand various crucial basic biology questions. Studies related to viruses are no exception to this. This simple eukaryotic organism is an invaluable model for studying fundamental cellular processes altered in the host cell due to viral infection or expression of viral proteins. Mechanisms of infection of several RNA and relatively few DNA viruses have been studied in yeast to date. Yeast is used for studying several aspects related to the replication of a virus, such as localization of viral proteins, interaction with host proteins, cellular effects on the host, etc. The development of novel techniques based on high-throughput analysis of libraries, availability of toolboxes for genetic manipulation, and a compact genome makes yeast a good choice for such studies. In this review, we provide an overview of the studies that have used yeast as a model system and have advanced our understanding of several important viruses. Key points• Yeast, a simple eukaryote, is an important model organism for studies related to viruses.• Several aspects of both DNA and RNA viruses of plants and animals are investigated using the yeast model.• Apart from the insights obtained on virus biology, yeast is also extensively used for antiviral development.

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“…Similar results were also observed upon expression of Hepatitis A virus 3C protease in S. cerevisiae. The authors report distortion and fragmentation of vacuole (Shubin et al 2021).…”

Section: Rna Virusesmentioning

confidence: 97%

Contribution of yeast models to virus research

Glingston

Yadav

Rajpoot

et al. 2021

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…Previously, we demonstrated that hepatitis A virus 3C protease (3Cpro) induces cell death that is also independent of caspase activity and features a unique cell morphology, specifically, the accumulation of cytoplasmic vacuoles with previously undocumented features. This suggested that the 3Cpro-induced cell death proceeds by an unknown pathway or is a new variant of a known RCD type [ 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Individual Expression of Hepatitis A Virus 3C Protease Induces Ferroptosis in Human Cells In Vitro

Komissarov

Karaseva

Roschina

et al. 2021

IJMS

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Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD, including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. Here, we expressed 3Cpro in HEK293, HeLa, and A549 human cell lines to characterize 3Cpro-induced cell death morphologically and biochemically using flow cytometry and fluorescence microscopy. We found that dead cells demonstrated necrosis-like morphological changes including permeabilization of the plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, we showed that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.

show abstract

“…Previously, we demonstrated that hepatitis A virus 3C protease (3Cpro) induces cell death, which is also independent of caspase activity and features a unique cell morphology, specifically, the accumulation of cytoplasmic vacuoles with previously undocumented features. This suggested that the 3Cpro-induced cell death proceeds by an unknown pathway or is a new variant of a known RCD type [10-12].…”

Section: Introductionmentioning

confidence: 99%