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 journalArticle

41 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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    Seidel, E., Le, V. T. K., Bar-On, Y., Tsukerman, P., Enk, J., Yamin, R., Stein, N., Schmiedel, D., OiknineDjian, E., Weisblum, Y., Tirosh, B., Stastny, P., Wolf, D. G., Hengel, H., & Mandelboim, O. (2015). Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA*008 to Escape Elimination by NK Cells. Cell Reports, 10(6), 968-982. https://doi.org/10.1016/j.celrep.2015.01.029