Murine cytomegalovirus m157 mutation and variation leads to immune evasion of natural killer cells

Valentina Voigt, Catherine A. Forbes, Joanne N. Tonkin, Mariapia A. Degli-Esposti, Hamish R.C. Smith, Wayne M. Yokoyama, Anthony A Scalzo

Research output: Contribution to journalArticleResearchpeer-review

158 Citations (Scopus)


Effective natural killer (NK) cell recognition of murine cytomegalovirus (MCMV)-infected cells depends on binding of the Ly49H NK cell activation receptor to the m157 viral glycoprotein. Here we addressed the immunological consequences of variation in m157 sequence and function. We found that most strains of MCMV possess forms of m157 that evade Ly49H-dependent NK cell activation. Importantly, repeated passage of MCMV through resistant Ly49H+ mice resulted in the rapid emergence of m157 mutants that elude Ly49H-dependent NK cell responses. These data provide the first molecular evidence that NK cells can exert sufficient immunological pressure on a DNA virus, such that it undergoes rapid and specific mutation in an NK cell ligand enabling it to evade efficient NK cell surveillance.

Original languageEnglish
Pages (from-to)13483-13488
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
Publication statusPublished - 11 Nov 2003
Externally publishedYes

Cite this