Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation
Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Advances in Virology |
| Online Access: | http://dx.doi.org/10.1155/2015/687162 |
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| author | Soren Gantt Eliora Gachelet Jacquelyn Carlsson Serge Barcy Corey Casper Michael Lagunoff |
| author_facet | Soren Gantt Eliora Gachelet Jacquelyn Carlsson Serge Barcy Corey Casper Michael Lagunoff |
| author_sort | Soren Gantt |
| collection | DOAJ |
| description | Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication. |
| format | Article |
| id | doaj-art-06cc98f21b5d451b9a3e6219c6068d92 |
| institution | Kabale University |
| issn | 1687-8639 1687-8647 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
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| series | Advances in Virology |
| spelling | doaj-art-06cc98f21b5d451b9a3e6219c6068d922025-02-03T01:00:34ZengWileyAdvances in Virology1687-86391687-86472015-01-01201510.1155/2015/687162687162Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus MaturationSoren Gantt0Eliora Gachelet1Jacquelyn Carlsson2Serge Barcy3Corey Casper4Michael Lagunoff5Seattle Children’s Research Institute, University of Washington, Seattle, WA 98101, USADepartment of Microbiology, University of Washington, Seattle, WA 98195, USADepartment of Medicine, University of Washington, Seattle, WA 98195, USASeattle Children’s Research Institute, University of Washington, Seattle, WA 98101, USADepartment of Global Health, University of Washington, Seattle, WA 98195, USADepartment of Microbiology, University of Washington, Seattle, WA 98195, USANelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.http://dx.doi.org/10.1155/2015/687162 |
| spellingShingle | Soren Gantt Eliora Gachelet Jacquelyn Carlsson Serge Barcy Corey Casper Michael Lagunoff Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation Advances in Virology |
| title | Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation |
| title_full | Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation |
| title_fullStr | Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation |
| title_full_unstemmed | Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation |
| title_short | Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation |
| title_sort | nelfinavir impairs glycosylation of herpes simplex virus 1 envelope proteins and blocks virus maturation |
| url | http://dx.doi.org/10.1155/2015/687162 |
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