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.
Highlights
Human herpesvirus-7 (HHV-7) is a T-lymphotrophic betaherpesvirus, most closely related to human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV)
While the cytomegaloviruses have demonstrated an extraordinary array of immunoevasive tactics, little is known about the immunoevasive strategies of the closely-related human herpesvirus-7 (HHV-7)
We have previously demonstrated that the U21 gene product from HHV-7 likely interferes with viral antigen presentation to cytotoxic T cells by rerouting class I major histocompatibility molecules to lysosomes for degradation
Summary
Human herpesvirus-7 (HHV-7) is a T-lymphotrophic betaherpesvirus, most closely related to human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV). HHV-7 remains latent or establishes persistent lifelong infections in its host. Herpesviruses have evolved numerous strategies to evade immune detection. Most herpesviruses, including HHV-7, have evolved mechanisms to interfere with viral antigen presentation by class I MHC molecules (for review see [2,3,4]). Preventing surface expression of class I MHC molecules may be an effective means of escaping CTL detection, the absence of class I products from the cell surface may render the host cell susceptible to Natural Killer (NK) cell attack (for review, see [5])
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