SEMINAR: Microbiology & Immunology Seminar Series: Revisiting the role of the MCMV-encoded m157 protein in NK cell anti-viral response

Dr Jerome Coudert, from the Lions Eye Institute, will give a talk on "Revisiting the role of the MCMV-encoded m157 protein in NK cell anti-viral response" in the Microbiology & Immunology Discipline Seminar room, Friday, 04 November 2011 at 9:00am. The Ly49H activating NK cell receptor in C57BL/6 (B6) mice plays a key role in early resistance to murine CMV (MCMV) infection through specific recognition of the MCMV-encoded MHC class I-like molecule m157 expressed on infected cells. The m157 gene is highly sequence variable among MCMV isolates, with many m157 variants unable to bind Ly49HB6. We sought to define if m157 variability alters the spectrum of interactions with other Ly49 molecules and if this modifies NK cell response and host susceptibility to MCMV. We have identified in the MCMV G1F strain, novel m157/Ly49 interactions involving Ly49C inhibitory NK cell receptors from B6 and BALB/c mouse background. Using an MCMV recombinant virus in which m157K181 was replaced with m157G1F, which interacts with both Ly49HB6 and Ly49CB6, we showed that the m157G1F/Ly49C interactions cause no apparent attenuating effect on viral clearance in B6 mice. However, when looking at the level of individual NK cells, m157 that can bind both inhibitory and activation receptors triggers a lesser NK cell activation. Thus, these data indicate that m157 variants that are able to interact with inhibitory Ly49 receptors in addition to activating receptors that are co-expressed on a same NK cell, can interfere with early NK cell responses. We will discuss how MCMV m157 variability differentially affects the antiviral NK cell response depending on the genetic background of the host, the MHC haplotype and the NK cell repertoire.