Abstract
Human cytomegalovirus (HCMV) is a major human pathogen, causing serious diseases in immunocompromised populations and congenially infected neonates. One of the main immune cells acting against the virus are Natural Killer (NK) cells. Killing by NK cells is mediated by a small family of activating receptors such as NKp30 that interact with the cellular ligand B7-H6. The outcome of B7-H6-NKp30 interaction was, so far, mainly studied with regard to NK recognition and killing of tumors. Here, we demonstrated that the expression of B7-H6 is upregulated following HCMV infection and that HCMV uses two of its genes: US18 and US20, to interfere with B7-H6 surface expression, in a mechanism involving endosomal degradation, in order to evade NK cell recognition.
Highlights
Human cytomegalovirus (HCMV), known as Human Herpesvirus 5 (HHV-5), is an important human pathogen, a member of the Betaherpesvirus family
In order to identify additional Natural Killer (NK) evasion mechanisms mediated by the US12 gene family, we infected primary Human Foreskin Fibroblast (HFF) cells with two strains of HCMV: a wild type TB40/e virus and a TB40/e mutant virus deleted for the US14-22 genomic region (ΔUS14-22). 96 hours following infection, the cells were stained for expression of various NK ligands
During the course of evolution and the arms race between HCMV and its human host, the virus has developed a large array of immune-evasion mechanisms, many of which are targeted against NK cell recognition of HCMV infected cells
Summary
HCMV, known as Human Herpesvirus 5 (HHV-5), is an important human pathogen, a member of the Betaherpesvirus family It infects the majority of the human population, and following primary infection, it can persists as a life-long infection[1]. NK cells have recently been classified as a cytotoxic type of Innate Lymphoid Cells (ILCs)[11] They constitute 5–15% of the lymphocytes in healthy peripheral blood, and are capable of killing virally-infected cells, tumor cells[12], bacteria[13, 14] and fungi[15]. The expression of NKG2D ligands, including the long and short alleles of MICA, is prevented during HCMV infection by both protein and microRNA-based mechanisms[8]. Known ligands of NKp30 include the Plasmodium falciparum protein PfEMP-121, the cellular nuclear factor BAT322, 23, and the cellular membrane protein B7-H624, while recognition of the HCMV protein pp[65] is inhibitory to NKp30-mediated killing[25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
