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

Kim Goldsmith, Wei Chen, David Johnson, Robert L. Hendricks

Research output: Contribution to journalArticle

106 Citations (Scopus)

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 vital protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalJournal of Experimental Medicine
Volume187
Issue number3
DOIs
StatePublished - Feb 2 1998

Fingerprint

Simplexvirus
T-Lymphocytes
Human Herpesvirus 1
Proteins
Nude Mice
Epithelium
Viruses
Cytoprotection
Peripheral Nervous System
Antigen Presentation
Sensory Receptor Cells
Epidermis
Mucous Membrane
Central Nervous System
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response. / Goldsmith, Kim; Chen, Wei; Johnson, David; Hendricks, Robert L.

In: Journal of Experimental Medicine, Vol. 187, No. 3, 02.02.1998, p. 341-348.

Research output: Contribution to journalArticle

@article{9ff89cc232ef4b1d8407a26deeff83c8,
title = "Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response",
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 vital protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.",
author = "Kim Goldsmith and Wei Chen and David Johnson and Hendricks, {Robert L.}",
year = "1998",
month = "2",
day = "2",
doi = "10.1084/jem.187.3.341",
language = "English (US)",
volume = "187",
pages = "341--348",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Infected cell protein (ICP)47 enhances herpes simplex virus neurovirulence by blocking the CD8+ T cell response

AU - Goldsmith, Kim

AU - Chen, Wei

AU - Johnson, David

AU - Hendricks, Robert L.

PY - 1998/2/2

Y1 - 1998/2/2

N2 - 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 vital protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.

AB - 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 vital protein shown to influence neurovirulence by inhibiting CD8+ T cell protection.

UR - http://www.scopus.com/inward/record.url?scp=0032472875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032472875&partnerID=8YFLogxK

U2 - 10.1084/jem.187.3.341

DO - 10.1084/jem.187.3.341

M3 - Article

C2 - 9449714

AN - SCOPUS:0032472875

VL - 187

SP - 341

EP - 348

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -