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 language | English (US) |
|---|---|
| Pages (from-to) | 341-348 |
| Number of pages | 8 |
| Journal | Journal of Experimental Medicine |
| Volume | 187 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 2 1998 |
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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 journal › Article
}
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.
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U2 - 10.1084/jem.187.3.341
DO - 10.1084/jem.187.3.341
M3 - Article
VL - 187
SP - 341
EP - 348
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 3
ER -