engleski

MCMV m04 functions as an NK cell response inhibitor

Mouse cytomegalovirus (MCMV), a β -herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. Its linear genome contains genes conserved among all herpesviruses, which are essential for viral replication, and also a palette of CMV and MCMV specific genes, mostly involved in an attempt to evade the host immune response. The best described, m145 family of genes, contains eight MHC class I-like proteins, out of which 4 (m145, m152, m155, m157) have already been proved as immunoevasins, exploiting different mechanisms with the same goal-to avoid recognition and attack from NK and T cells. Functions attributed to some family members include downregulation of host MHC-I (m152) and NKG2D ligands (m145, m152, m155) and interaction with inhibitory or activating NK receptors (m157). Beside the above mentioned m152, MCMV encodes m04 and m06 which are also described to interfere with the ability of cytotoxic T cells to detect virus-infected fibroblasts. While m06/gp48 is shown to cause degradation of MHC class I molecules, m04/gp34 is originally described as a NK cell decoy, although never actually proved so. Nevertheless, m04/gp34 shows some unique features while interfering with antigen presentation. It is found in association with MHC class I molecules on the cell surface, and does not reduce the amount of these molecules from the surface of infected cells. Here we want to present the ability of m04/gp34 to serve as an inhibitor of NK cell response in vivo in a haplotype dependent fashion. Namely, we observed that the MCMV virus lacking the m04 gene is better controlled (attenuated by app. 2 log difference) by the host than the wild type virus and that this feature is completely due to the NK cell response since it is reversed after NK cell depletion. This phenomenon is attributed to mice of H-2d (Balb/c mice) and H-2k (C3H and CBA mice) haplotype, but not of H-2b. Since we were able to determine that the m04/gp34 does not affect the surface expression of NKG2D ligands our future studies are aimed to investigate the relationship of m04 and other NK cell receptors.

MCMV; NK Cell; m04

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