engleski

Immunosurveilance of recombinant MCMV expressing NKG2D ligand RAE-1gamma

Natural killer (NK) cells offer early antiviral protection. Their dominant activating receptor is NKG2D, also present as a co-receptor on CD8+ T cells. Its role in the function of CD8+ T cells is still insufficiently defined. NKG2D ligands ; MULT-1, RAE-1 and H60 in mice, expressed on the surface of stressed or infected cells, are down-regulated by several mouse cytomegalovirus (MCMV) immunoevasins (m138, m145, m152, and m155). Deletion of any of these viral genes results in NKG2D- dependent virus attenuation in vivo. We aimed to study the influence of permanent engagement of NKG2D receptor on the viral control. For that purpose we generated the virus containing the gene for RAE-1gamma but lacking the gene for m152, thus enabling continuous expression of RAE-1gamma. First we tested the Delta-m152-RAE-1gamma in vitro and confirmed the presence of RAE-1gamma on the surface of infected cells. Next, we followed the viral titer in various organs of mice infected with wild type (WT) or Delta-m152-RAE-1gamma up to 200 days post infection. The results have showed the Delta-m152-RAE-1gamma virus to be heavily attenuated in NK cell dependent manner. Antigen specific CD8+ T cells isolated from WT MCMV or Delta-m152-RAE-1gamma infected animals had no gross difference in respect to expression of markers for effector memory T cells or IFNgamma production. Further studies are aimed to investigate the impact of constitutive expression of NKG2D ligand on infected cells onto the maintenance of antiviral immunity and viral genome load during latent/chronic infection, as well as the capacity of the virus to reactivate from latency.

NKG2D; MCMV

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