Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells

Einat Seidel, Vu Thuy Khanh Le, Yotam Bar-On, Pinchas Tsukerman, Jonatan Enk, Rachel Yamin, Natan Stein, Dominik Schmiedel, Esther OiknineDjian, Yiska Weisblum, Boaz Tirosh, Peter Stastny, Dana G. Wolf, Hartmut Hengel, Ofer Mandelboim

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA*008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA*008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host alleleillustrates the dynamic co-evolution of host and pathogen.

Original languageEnglish (US)
Pages (from-to)968-982
Number of pages15
JournalCell Reports
Volume10
Issue number6
DOIs
StatePublished - Feb 17 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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