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Advances in Virology
Volume 2015, Article ID 687162, 9 pages
http://dx.doi.org/10.1155/2015/687162
Research Article

Nelfinavir Impairs Glycosylation of Herpes Simplex Virus 1 Envelope Proteins and Blocks Virus Maturation

1Seattle Children’s Research Institute, University of Washington, Seattle, WA 98101, USA
2Department of Pediatrics, University of Washington, Seattle, WA 98105, USA
3Department of Global Health, University of Washington, Seattle, WA 98195, USA
4Department of Microbiology, University of Washington, Seattle, WA 98195, USA
5Department of Medicine, University of Washington, Seattle, WA 98195, USA
6Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
7Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

Received 7 October 2014; Revised 8 January 2015; Accepted 12 January 2015

Academic Editor: Gary S. Hayward

Copyright © 2015 Soren Gantt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.