A herpesvirus encoded Qa-1 mimic inhibits natural killer cell cytotoxicity through CD94/NKG2A receptor engagement

Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of ‘missing-self’ recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, pQa-1 selectively inhibits NKG2A + NK cells and expression of pQa-1 can protect tumor cells from NK control in vivo. Collectively, these findings reveal an innovative NK evasion strategy wherein RHVP encodes a modified Qa-1 mimic refractory to MHC-I sabotage and capable of specifically engaging inhibitory receptors to circumvent NK activation. DOI: https://doi.org/10.7554/eLife.38667.001.

Original languageEnglish
Article numbere38667
JournaleLife
Volume7
DOIs
StatePublished - Dec 1 2018

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