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Differential regulation of MHC class-I-restricted and unrestricted cytotoxicity by the Us3 protein kinase of herpes simplex virus-1.

Abstract：

:Modulation of cytotoxic responses by viral immunoevasins plays an important role in the establishment of latent and persistent viral infections. Together with MHC class-I-restricted CD8T-lymphocytes, non-MHC-restricted natural killer (NK) and lymphokine-activated killer (LAK) cells participate in this anti-viral control. The Us3 protein kinase of herpes simplex virus-1 (HSV-1) inhibits CD8T-cell cytotoxicity, which correlates with the inhibition of granzyme-B (GrB)-induced activation of pro-apoptotic Bid. We have investigated the effect of Us3 on NK and LAK cytotoxicity, because these effectors are believed to share common mechanisms for inducing cell death. We show that, in contrast to their lower sensitivity to CD8T-cell lysis, HSV-1-infected cells are lysed by NK cells or LAK cells as efficiently as the uninfected controls. Both CD8T and NK/LAK effectors were dependent on the activity of GrB and were efficiently blocked by means of treatment with a GrB inhibitor. However, unlike CD8T cells, LAK cells and NK cells failed to induce Bid cleavage, suggesting that various GrB downstream targets be involved in the induction of cell lysis. This finding explains their various sensitivities to viral modulation, which is likely to be important for the respective role of MHC-restricted and non-restricted effectors in the control of HSV-1 infection.

journal_name

Scand J Immunol

journal_title

Scandinavian journal of immunology

authors

Cartier A,Masucci MG

doi

10.1111/j.0300-9475.2004.01523.x

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

592-9

issue

6

eissn

0300-9475

issn

1365-3083

pii

SJI1523

journal_volume

60

pub_type

杂志文章

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