engleski

In vivo potential of m152 gene of murine cytomegalovirus to evade control by MHC class I restricted T cells

Introduction: The murine cytomegalovirus (MCMV) glycoprotein encoded by the m152 gene blocks export of MHC class I complexes from the ER-GIS/cis-Golgi compartment, and thereby prevent presentation of viral antigens to cytotoxic T lymphocites. Material and Methods: A recombinant MCMV strain harboring a deletion of the m152 gene and the corresponding recombinant revertant strain were used to investigate the biological relevance of these gene product. Recombint viruses were produced using cre-loxP recombination system and selected on the basis of lacZ gene expression. Results: Deletion of the m152 gene had no effect on virus growth in primary fibroblasts cell culture. However, the deletion strain reached lower peak titers and exibited an attenuated disease course in newborn Balb/c mice. To determine if the m152 deletion strain is more susceptible to immune control, growth of the recombinant strains was examined in MHC class I-deficient ƒŇ2-/- mice. The deletion and revertant recombinant strains exibited equivalent virus titer profiles in ƒŇ2-/- mice. Additionaly, no difference in virus growth between these strains was observed in 4-day old mice depleted of T cells and NK cells. Furthermore, adoptive transfer experiments suggest that the m152 gene product functions by interfering with T cell priming in both primary and secondary immune responses. These studies indicate a role for the m152 gene product in evasion of the MHC class I restricted immune control.

antigen presentation; ER retention; m152; MHC class I; murine cytomegalovirus

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