Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication
The participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2023-12-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/3977 |
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| author | E. L. Mishchenko A. A. Makarova E. A. Antropova A. S. Venzel T. V. Ivanisenko P. S. Demenkov V. A. Ivanisenko |
| author_facet | E. L. Mishchenko A. A. Makarova E. A. Antropova A. S. Venzel T. V. Ivanisenko P. S. Demenkov V. A. Ivanisenko |
| author_sort | E. L. Mishchenko |
| collection | DOAJ |
| description | The participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of drug resistance to the existing drugs remain the main obstacles to fighting HCV. Identifying the host factors, exploring their role in HCV RNA replication, and studying viral effects on their expression is essential for understanding the mechanisms of viral replication and developing novel, effective curative approaches. It is known that the host factors PREB (prolactin regulatory element binding) and PLA2G4C (cytosolic phospholipase A2 gamma) are important for the functioning of the viral replicase complex and the formation of the platforms of HCV genome replication. The expression of PREB and PLA2G4C was significantly elevated in the presence of the HCV genome. However, the mechanisms of its regulation by HCV remain unknown. In this paper, using a text-mining technology provided by ANDSystem, we reconstructed and analyzed gene networks describing regulatory effects on the expression of PREB and PLA2G4C by HCV proteins. On the basis of the gene network analysis performed, we put forward hypotheses about the modulation of the host factors functions resulting from protein-protein interaction with HCV proteins. Among the viral proteins, NS3 showed the greatest number of regulatory linkages. We assumed that NS3 could inhibit the function of host transcription factor (TF) NOTCH1 by protein-protein interaction, leading to upregulation of PREB and PLA2G4C. Analysis of the gene networks and data on differential gene expression in HCV-infected cells allowed us to hypothesize further how HCV could regulate the expression of TFs, the binding sites of which are localized within PREB and PLA2G4C gene regions. The results obtained can be used for planning studies of the molecular-genetic mechanisms of viral-host interaction and searching for potential targets for anti-HCV therapy. |
| format | Article |
| id | doaj-art-1032012513db4a30adcde09c9a1e092f |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-1032012513db4a30adcde09c9a1e092f2025-02-01T09:58:12ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592023-12-0127777678310.18699/VJGB-23-901405Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replicationE. L. Mishchenko0A. A. Makarova1E. A. Antropova2A. S. Venzel3T. V. Ivanisenko4P. S. Demenkov5V. A. Ivanisenko6Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RAS; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RAS; Novosibirsk State UniversityThe participants of Hepatitis C virus (HCV) replication are both viral and host proteins. Therapeutic approaches based on activity inhibition of viral non-structural proteins NS3, NS5A, and NS5B are undergoing clinical trials. However, rapid mutation processes in the viral genome and acquisition of drug resistance to the existing drugs remain the main obstacles to fighting HCV. Identifying the host factors, exploring their role in HCV RNA replication, and studying viral effects on their expression is essential for understanding the mechanisms of viral replication and developing novel, effective curative approaches. It is known that the host factors PREB (prolactin regulatory element binding) and PLA2G4C (cytosolic phospholipase A2 gamma) are important for the functioning of the viral replicase complex and the formation of the platforms of HCV genome replication. The expression of PREB and PLA2G4C was significantly elevated in the presence of the HCV genome. However, the mechanisms of its regulation by HCV remain unknown. In this paper, using a text-mining technology provided by ANDSystem, we reconstructed and analyzed gene networks describing regulatory effects on the expression of PREB and PLA2G4C by HCV proteins. On the basis of the gene network analysis performed, we put forward hypotheses about the modulation of the host factors functions resulting from protein-protein interaction with HCV proteins. Among the viral proteins, NS3 showed the greatest number of regulatory linkages. We assumed that NS3 could inhibit the function of host transcription factor (TF) NOTCH1 by protein-protein interaction, leading to upregulation of PREB and PLA2G4C. Analysis of the gene networks and data on differential gene expression in HCV-infected cells allowed us to hypothesize further how HCV could regulate the expression of TFs, the binding sites of which are localized within PREB and PLA2G4C gene regions. The results obtained can be used for planning studies of the molecular-genetic mechanisms of viral-host interaction and searching for potential targets for anti-HCV therapy.https://vavilov.elpub.ru/jour/article/view/3977hepatitis c virushcv gene replicationreplicase hcvhost factorsgene networksphospholipase pla2g4cpreb protein |
| spellingShingle | E. L. Mishchenko A. A. Makarova E. A. Antropova A. S. Venzel T. V. Ivanisenko P. S. Demenkov V. A. Ivanisenko Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication Вавиловский журнал генетики и селекции hepatitis c virus hcv gene replication replicase hcv host factors gene networks phospholipase pla2g4c preb protein |
| title | Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication |
| title_full | Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication |
| title_fullStr | Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication |
| title_full_unstemmed | Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication |
| title_short | Molecular-genetic pathways of hepatitis C virus regulation of the expression of cellular factors PREB and PLA2G4C, which play an important role in virus replication |
| title_sort | molecular genetic pathways of hepatitis c virus regulation of the expression of cellular factors preb and pla2g4c which play an important role in virus replication |
| topic | hepatitis c virus hcv gene replication replicase hcv host factors gene networks phospholipase pla2g4c preb protein |
| url | https://vavilov.elpub.ru/jour/article/view/3977 |
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