Inhibitors of signal peptide peptidase (SPP) affect HSV-1 infectivity in vitro and in vivo.

Abstract	Recently we have shown that the highly conserved herpes simplex virus glycoprotein K (gK) binds to signal peptide peptidase (SPP), also known as minor histocompatibility antigen H13. In this study we have demonstrated for the first time that inhibitors of SPP, such as L685,458, (Z-LL)2 ketone, aspirin, ibuprofen and DAPT, significantly reduced HSV-1 replication in tissue culture. Inhibition of SPP activity via (Z-LL)2 ketone significantly reduced viral transcripts in the nucleus of infected cells. Finally, when administered during primary infection, (Z-LL)2 ketone inhibitor reduced HSV-1 replication in the eyes of ocularly infected mice. Thus, blocking SPP activity may represent a clinically effective and expedient approach to the reduction of viral replication and the resulting pathology.
Authors	Sariah J Allen, Kevin R Mott, Homayon Ghiasi
Journal	Experimental eye research (Exp Eye Res) Vol. 123 Pg. 8-15 (Jun 2014) ISSN: 1096-0007 [Electronic] England
PMID	24768597 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright	Copyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References	1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone Carbamates DNA, Viral Dipeptides Enzyme Inhibitors L 685458 N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester Ophthalmic Solutions RNA, Messenger Aspartic Acid Endopeptidases signal peptide peptidase Aspirin Ibuprofen
Topics	Animals Aspartic Acid Endopeptidases (antagonists & inhibitors) Aspirin (pharmacology) Carbamates (pharmacology) Cell Fractionation Cells, Cultured DNA, Viral (genetics) Dipeptides (pharmacology) Disease Models, Animal Enzyme Inhibitors (pharmacology) Female Gene Expression Regulation, Viral (physiology) Herpesvirus 1, Human (genetics, pathogenicity, physiology) Ibuprofen (pharmacology) Keratitis, Herpetic (prevention & control, virology) Mice Mice, Inbred BALB C Mice, Inbred C57BL Ophthalmic Solutions RNA, Messenger (metabolism) Rabbits Real-Time Polymerase Chain Reaction Skin (cytology, virology) Virus Replication (drug effects)

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