engleski

MURINE CYTOMEGALOVIRUS m04/gp34 IS NK CELL DECOY

Both human and murine cytomegaloviruses (CMVs) encode multiple genes that interfere with MHC class I antigen presentation and thus protect infected cells from lysis by CD8+ cytotoxic T lymphocytes. In murine CMV (MCMV) three immune-evasion genes which interfere with MHC class I antigen presentation have been identified so far: m06, m152 and m04. Yet, down-modulation of MHC I molecules should expose infected cells to NK cell lysis since these molecules also serve as ligands for inhibitory NK cell receptors. Gp34 is type I transmembrane protein encoded by m04, a member of the MCMV m02 gene family. In the endoplasmic reticulum (ER) it binds to class I molecule and forms a complex which is exported through the Golgi compartment to the cell surface. It has been speculated that m04 serves to oppose the action of m152 and m06 by rescuing some class I molecules from retention in ER, thus protecting infected cells from NK cells. Here we report that m04-deletion mutant virus is attenuated in vivo three days postinfection in NK-cell dependent manner. The attenuation of m04 deletion mutant was detected in BALB/c (H2d) and DBA (H2d) mice, but not in BALB/B (H2b) and 129/SvJ (H2b) mice. Moreover, attenuation was not observed in BALB/c TAP1-/- mouse strain, indicating that effect of m04/gp34 on NK cell control is TAP1 and MHC class I dependent.

cytomegalovirus; NK cells; m04 gene; decoy

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