Role of the vacuolar ATPase in the Alphavirus replication cycle
We have shown that Alphaviruses can enter cells by direct penetration at the plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J Virol, 87:4352–4359, 2013). Direct penetration removes the requirement for receptor-mediated endocytosis exposure to low pH and membrane fusio...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-07-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844018324307 |
| _version_ | 1818265316765990912 |
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| author | Ryan M. Schuchman Ricardo Vancini Amanda Piper Denitra Breuer Mariana Ribeiro Davis Ferreira Joseph Magliocca Veronica Emmerich Raquel Hernandez Dennis T. Brown |
| author_facet | Ryan M. Schuchman Ricardo Vancini Amanda Piper Denitra Breuer Mariana Ribeiro Davis Ferreira Joseph Magliocca Veronica Emmerich Raquel Hernandez Dennis T. Brown |
| author_sort | Ryan M. Schuchman |
| collection | DOAJ |
| description | We have shown that Alphaviruses can enter cells by direct penetration at the plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J Virol, 87:4352–4359, 2013). Direct penetration removes the requirement for receptor-mediated endocytosis exposure to low pH and membrane fusion in the process of RNA entry. Endosomal pH as well as the pH of the cell cytoplasm is maintained by the activity of the vacuolar ATPase (V-ATPase). Bafilomycin is a specific inhibitor of V-ATPase. To characterize the roll of the V-ATPase in viral replication we generated a Bafilomycin A1(BAF) resistant mutant of Sindbis virus (BRSV). BRSV produced mature virus and virus RNA in greater amounts than parent virus in BAF-treated cells. Sequence analysis revealed mutations in the E2 glycoprotein, T15I/Y18H, were responsible for the phenotype. These results show that a functional V-ATPase is required for efficient virus RNA synthesis and virus maturation in Alphavirus infection. |
| first_indexed | 2024-12-12T19:48:52Z |
| format | Article |
| id | doaj.art-f6f43992cf2e4c0ea085856c28e65987 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-12T19:48:52Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f6f43992cf2e4c0ea085856c28e659872022-12-22T00:14:02ZengElsevierHeliyon2405-84402018-07-0147e00701Role of the vacuolar ATPase in the Alphavirus replication cycleRyan M. Schuchman0Ricardo Vancini1Amanda Piper2Denitra Breuer3Mariana Ribeiro4Davis Ferreira5Joseph Magliocca6Veronica Emmerich7Raquel Hernandez8Dennis T. Brown9Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA; Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, BrazilDepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USADepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA; Corresponding author.We have shown that Alphaviruses can enter cells by direct penetration at the plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J Virol, 87:4352–4359, 2013). Direct penetration removes the requirement for receptor-mediated endocytosis exposure to low pH and membrane fusion in the process of RNA entry. Endosomal pH as well as the pH of the cell cytoplasm is maintained by the activity of the vacuolar ATPase (V-ATPase). Bafilomycin is a specific inhibitor of V-ATPase. To characterize the roll of the V-ATPase in viral replication we generated a Bafilomycin A1(BAF) resistant mutant of Sindbis virus (BRSV). BRSV produced mature virus and virus RNA in greater amounts than parent virus in BAF-treated cells. Sequence analysis revealed mutations in the E2 glycoprotein, T15I/Y18H, were responsible for the phenotype. These results show that a functional V-ATPase is required for efficient virus RNA synthesis and virus maturation in Alphavirus infection.http://www.sciencedirect.com/science/article/pii/S2405844018324307VirologyCell biology |
| spellingShingle | Ryan M. Schuchman Ricardo Vancini Amanda Piper Denitra Breuer Mariana Ribeiro Davis Ferreira Joseph Magliocca Veronica Emmerich Raquel Hernandez Dennis T. Brown Role of the vacuolar ATPase in the Alphavirus replication cycle Heliyon Virology Cell biology |
| title | Role of the vacuolar ATPase in the Alphavirus replication cycle |
| title_full | Role of the vacuolar ATPase in the Alphavirus replication cycle |
| title_fullStr | Role of the vacuolar ATPase in the Alphavirus replication cycle |
| title_full_unstemmed | Role of the vacuolar ATPase in the Alphavirus replication cycle |
| title_short | Role of the vacuolar ATPase in the Alphavirus replication cycle |
| title_sort | role of the vacuolar atpase in the alphavirus replication cycle |
| topic | Virology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844018324307 |
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