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MHC Class I-Subversive Gene Functions of Cytomegalovirus and their Regulation by Interferons-an Intricate Balance

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Book cover Molecular Evolution of Viruses — Past and Present

Abstract

Multiple glycoproteins of human cytomegalovirus (HCMV) encoded by the genes US2, US3, US6 and US11 interrupt the MHC class I pathway of antigen presentation at distinct checkpoints to avoid recognition of infected cells by cytotoxic CD8+ T lymphocytes. The action of cytokines like interferon (IFN)-γ, IFN-α/β and tumour necrosis factor α (TNF-α) compensate for the viral inhibition and restore antigen presentation in HCMV-infected cells. This finding was explained by their effects on cellular rather than viral genes and reflected by an increase in the production, assembly and maturation of MHC class I molecules resulting in an escape of MHC I from viral control. Here we reproduce the IFN-γ-mediated effect when MHC I-subversive gene functions of HCMV are tested in isolation, but the efficacy of IFN-γ to restore MHC I surface expression in US2-, US6- and US11-transfectants differs significantly. In addition, in HCMV-infected cells IFN-γ strongly affects the synthesis of the US6-encoded glycoprotein. Despite the capability of HCMV to block the interferon signaling pathway the IFN-γ driven enhancement of MHC class I and class II expression remains effective provided that cells are exposed to IFN-γ before infection. Our findings illustrate a complex interplay between host immune factors and viral immune evasion functions.

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Author information

Author notes

  1. Hartmut Hengel

    Present address: Robert Koch-Institut, POB 650280, D-13302, Berlin, Germany

Authors and Affiliations

  1. Max von Pettenkofer-Institut, Lehrstuhl Virologie, Ludwig-Maximillians-Universität München, Pettenkoferstr, 9a D-80336, München, Germany

    Christine Benz & Hartmut Hengel

Authors
  1. Christine Benz
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  2. Hartmut Hengel
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Editor information

Editors and Affiliations

  1. Department of Molecular Virology, The Hebrew University of Jerusalem, Jerusalem, Israel

    Yechiel Becker

  2. Institute of Medical Virology, Ruprecht-Karls University, Heidelberg, Germany

    Gholamreza Darai

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Benz, C., Hengel, H. (2000). MHC Class I-Subversive Gene Functions of Cytomegalovirus and their Regulation by Interferons-an Intricate Balance. In: Becker, Y., Darai, G. (eds) Molecular Evolution of Viruses — Past and Present. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1707-8_4

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  • DOI: https://doi.org/10.1007/978-1-4615-1707-8_4

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  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5688-2

  • Online ISBN: 978-1-4615-1707-8

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