PMID: 9449714Mar 21, 1998Paper

Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response

The Journal of Experimental Medicine
K GoldsmithRobert L Hendricks

Abstract

The herpes simplex virus (HSV) infected cell protein (ICP)47 blocks CD8+ T cell recognition of infected cells by inhibiting the transporter associated with antigen presentation (TAP). In vivo, HSV-1 replicates in two distinct tissues: in epithelial mucosa or epidermis, where the virus enters sensory neurons; and in the peripheral and central nervous system, where acute and subsequently latent infections occur. Here, we show that an HSV-1 ICP47- mutant is less neurovirulent than wild-type HSV-1 in mice, but replicates normally in epithelial tissues. The reduced neurovirulence of the ICP47- mutant was due to a protective CD8+ T cell response. When compared with wild-type virus, the ICP47- mutant expressed reduced neurovirulence in immunologically normal mice, and T cell-deficient nude mice after reconstitution with CD8+ T cells. However, the ICP47- mutant exhibited normal neurovirulence in mice that were acutely depleted of CD8+ T cells, and in nude mice that were not reconstituted, or were reconstituted with CD4+ T cells. In contrast, CD8+ T cell depletion did not increase the neurovirulence of an unrelated, attenuated HSV-1 glycoprotein (g)E- mutant. ICP47 is the first viral protein shown to influence neurovirulence by inhibiti...Continue Reading

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Citations

Jan 15, 2000·Advances in Internal Medicine·A R Marques, S E Straus
Mar 16, 2000·Developmental and Comparative Immunology·K A Schat, Z Xing
Feb 27, 1999·Current Opinion in Immunology·D M Miller, D D Sedmak
Mar 6, 1999·Current Opinion in Microbiology·M B Oldstone
Jun 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cathie G Miller, Nigel W Fraser
Feb 17, 1999·The Journal of Experimental Medicine·D A LeibH W Virgin
Oct 11, 2005·Viral Immunology·Vilma DecmanRobert L Hendricks
Jan 15, 2003·Clinical Microbiology Reviews·Clinton Jones
Jan 15, 2003·Clinical Microbiology Reviews·David M Koelle, Lawrence Corey
May 10, 2000·Proceedings of the National Academy of Sciences of the United States of America·D A LeibH W Virgin
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·T TodoP A Johnson
Feb 20, 2010·Interdisciplinary Perspectives on Infectious Diseases·Guey-Chuen Perng, Clinton Jones
Sep 5, 2012·Progress in Retinal and Eye Research·A M RoweR L Hendricks
Jun 11, 2009·Scandinavian Journal of Immunology·D SchepisL Berg
Feb 28, 2013·Human Vaccines & Immunotherapeutics·Jeffrey L Coleman, Deepak Shukla

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