KFU. Card publication. Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics

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FEDERAL UNIVERSITY

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ANTI-INFLUENZA ACTIVITY OF THE RIBONUCLEASE BINASE: CELLULAR TARGETS DETECTED BY QUANTITATIVE PROTEOMICS

Form of presentation

Articles in international journals and collections

Year of publication

2020

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Authors, employees of KFU

Dudkina Elena Vladimirovna, author

Ilinskaya Olga Nikolaevna, author

Laykov Aleksandr Vladimirovich, author

Markelova Mariya Ivanovna, author

Ulyanova Vera Vladimirovna, author

Shakh Makhmud Raikhan , author

Bibliographic description in the original language

Ulyanova, V.; Shah Mahmud, R.; Laikov, A.; Dudkina, E.; Markelova, M.; Mostafa, A.; Pleschka, S.; Ilinskaya, O. Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics. Int. J. Mol. Sci. 2020, 21, 8294.

Annotation

Unpredictable influenza pandemics, annual epidemics, and sporadic poultry-to-human avian influenza virus infections with high morbidity and mortality rates dictate a need to develop new antiviral approaches. Targeting cellular pathways and processes is a promising antiviral strategy shown to be effective regardless of viral subtypes or viral evolution of drug-resistant variants. Proteomics-based searches provide a tool to reveal the druggable stages of the virus life cycle and to understand the putative antiviral mode of action of the drug(s). Ribonucleases (RNases) of different origins not only demonstrate antiviral effects that are mediated by the direct RNase action on viral and cellular RNAs but can also exert their impact by signal transduction modulation. To our knowledge, studies of the RNase-affected cell proteome have not yet been performed. To reveal cellular targets and explain the mechanisms underlying the antiviral effect employed by the small extra-cellular ribonuclease of Bacillus pumilus (binase) both in vitro and in vivo, qualitative shotgun and quantitative targeted proteomic analyses of the influenza A virus (IAV) H1N1pdm09-infected A549 cells upon binase treatment were performed. We compared proteomes of mock-treated, binase-treated, virus-infected, and virus-infected binase-treated cells to determine the proteins affected by IAV and/or binase. In general, IAV demonstrated a downregulating strategy towards cellular proteins, while binase had an upregulating effect. With the help of bioinformatics approaches, coregulated cellular protein sets were defined and assigned to their biological function; a possible interconnection with the progression of viral infection was conferred. Most of the proteins downregulated by IAV (e.g., AKR1B1, AKR1C1, CCL5, PFN1, RAN, S100A4, etc.) belong to the processes of cellular metabolism, response to stimulus, biological regulation, and cellular localization. Upregulated proteins upon the binase treatment (e.g., AKR1B10, CAP1, HNRNPA2B1, PFN1, PPIA, YWHAB, etc.) are united by the processes of biological regulation, cellular localization, and immune and metabolic processes. The antiviral activity of binase against IAV was expressed by the inversion of virus-induced proteomic changes, resulting in the inhibition of virus-associated processes, including nuclear ribonucleoprotein export (NCL, NPM1, Nup205, and Bax proteins involved) and cytoskeleton remodeling (RDX, PFN1, and TUBB) induced by IAV at the middle stage of single-cycle infection in A549 cells. Modulation of the immune response could be involved as well. Overall, it seems possible that binase exerts its antiviral effects in multiple ways.

Keywords

influenza virus; ribonuclease; binase; antiviral activity; proteomics; liquid chromatography-tandem mass spectrometry (LC-MS/MS); multiple reaction monitoring (MRM)

The name of the journal

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663932/

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=243752&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Dudkina Elena Vladimirovna	ru_RU
dc.contributor.author	Ilinskaya Olga Nikolaevna	ru_RU
dc.contributor.author	Laykov Aleksandr Vladimirovich	ru_RU
dc.contributor.author	Markelova Mariya Ivanovna	ru_RU
dc.contributor.author	Ulyanova Vera Vladimirovna	ru_RU
dc.contributor.author	Shakh Makhmud Raikhan	ru_RU
dc.date.accessioned	2020-01-01T00:00:00Z	ru_RU
dc.date.available	2020-01-01T00:00:00Z	ru_RU
dc.date.issued	2020	ru_RU
dc.identifier.citation	Ulyanova, V.; Shah Mahmud, R.; Laikov, A.; Dudkina, E.; Markelova, M.; Mostafa, A.; Pleschka, S.; Ilinskaya, O. Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics. Int. J. Mol. Sci. 2020, 21, 8294.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=243752&p_lang=2	ru_RU
dc.description.abstract	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES	ru_RU
dc.description.abstract	Unpredictable influenza pandemics, annual epidemics, and sporadic poultry-to-human avian influenza virus infections with high morbidity and mortality rates dictate a need to develop new antiviral approaches. Targeting cellular pathways and processes is a promising antiviral strategy shown to be effective regardless of viral subtypes or viral evolution of drug-resistant variants. Proteomics-based searches provide a tool to reveal the druggable stages of the virus life cycle and to understand the putative antiviral mode of action of the drug(s). Ribonucleases (RNases) of different origins not only demonstrate antiviral effects that are mediated by the direct RNase action on viral and cellular RNAs but can also exert their impact by signal transduction modulation. To our knowledge, studies of the RNase-affected cell proteome have not yet been performed. To reveal cellular targets and explain the mechanisms underlying the antiviral effect employed by the small extra-cellular ribonuclease of Bacillus pumilus (binase) both in vitro and in vivo, qualitative shotgun and quantitative targeted proteomic analyses of the influenza A virus (IAV) H1N1pdm09-infected A549 cells upon binase treatment were performed. We compared proteomes of mock-treated, binase-treated, virus-infected, and virus-infected binase-treated cells to determine the proteins affected by IAV and/or binase. In general, IAV demonstrated a downregulating strategy towards cellular proteins, while binase had an upregulating effect. With the help of bioinformatics approaches, coregulated cellular protein sets were defined and assigned to their biological function; a possible interconnection with the progression of viral infection was conferred. Most of the proteins downregulated by IAV (e.g., AKR1B1, AKR1C1, CCL5, PFN1, RAN, S100A4, etc.) belong to the processes of cellular metabolism, response to stimulus, biological regulation, and cellular localization. Upregulated proteins upon the binase treatment (e.g., AKR1B10, CAP1, HNRNPA2B1, PFN1, PPIA, YWHAB, etc.) are united by the processes of biological regulation, cellular localization, and immune and metabolic processes. The antiviral activity of binase against IAV was expressed by the inversion of virus-induced proteomic changes, resulting in the inhibition of virus-associated processes, including nuclear ribonucleoprotein export (NCL, NPM1, Nup205, and Bax proteins involved) and cytoskeleton remodeling (RDX, PFN1, and TUBB) induced by IAV at the middle stage of single-cycle infection in A549 cells. Modulation of the immune response could be involved as well. Overall, it seems possible that binase exerts its antiviral effects in multiple ways.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics	ru_RU
dc.type	Articles in international journals and collections	ru_RU