HHV-6 and Natural Killer Cells
P.P. Banerjee on IFN-gamma-Dependent
Demyelinating Activity by Natural Killer Cells is Regulated by HLA-G
Upregulation on Oligodendrocytes During HHV-6 Infection.
HHV-6
Modulates Natural Killer Cells Via IL-15 Production
HHV-7 and Natural Killer Cells
The Human
Herpesvirus-7 (HHV-7) U21 Immunoevasin Subverts NK-Mediated Cytoxicity through
Modulation of MICA and MICB
Christine L.
Schneider and Amy W. Hudson
Abstract
Herpesviruses have
evolved numerous immune evasion strategies to facilitate establishment of lifelong
persistent infections. Many herpesviruses encode gene products devoted to
preventing viral antigen presentation as a means of escaping detection by
cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 gene product, for
example, is an immunoevasin that binds to class I major histocompatibility
complex molecules and redirects them to the lysosomal compartment. Virus
infection can also induce the upregulation of surface ligands that activate NK
cells. Accordingly, the herpesviruses have evolved a diverse array of
mechanisms to prevent NK cell engagement of NK-activating ligands on
virus-infected cells. Here we demonstrate that the HHV-7 U21 gene product
interferes with NK recognition. U21 can bind to the NK activating ligand ULBP1
and reroute it to the lysosomal compartment. In addition, U21 downregulates the
surface expression of the NK activating ligands MICA and MICB, resulting in a
reduction in NK-mediated cytotoxicity. These results suggest that this single
viral protein may interfere both with CTL-mediated recognition through the
downregulation of class I MHC molecules as well as NK-mediated recognition
through downregulation of NK activating ligands.
The
Human Herpesvirus-7 (HHV-7) U21 Immunoevasin Subverts NK-Mediated Cytoxicity
through Modulation of MICA and MICB
Christine L.
Schneider, Amy W. Hudson
Department of
Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee,
Wisconsin, United States of America
Abstract
Herpesviruses have
evolved numerous immune evasion strategies to facilitate establishment of
lifelong persistent infections. Many herpesviruses encode gene products devoted
to preventing viral antigen presentation as a means of escaping detection by
cytotoxic T lymphocytes. The human herpesvirus-7 (HHV-7) U21 gene product, for
example, is an immunoevasin that binds to class I major histocompatibility
complex molecules and redirects them to the lysosomal compartment. Virus
infection can also induce the upregulation of surface ligands that activate NK
cells. Accordingly, the herpesviruses have evolved a diverse array of
mechanisms to prevent NK cell engagement of NK-activating ligands on
virus-infected cells. Here we demonstrate that the HHV-7 U21 gene product
interferes with NK recognition. U21 can bind to the NK activating ligand ULBP1
and reroute it to the lysosomal compartment. In addition, U21 downregulates the
surface expression of the NK activating ligands MICA and MICB, resulting in a
reduction in NK-mediated cytotoxicity. These results suggest that this single
viral protein may interfere both with CTL-mediated recognition through the
downregulation of class I MHC molecules as well as NK-mediated recognition
through downregulation of NK activating ligands.
