engleski

The product of m152 gene enables murine cytomegalovirus to evade control by MHC class I restricted T lymphocytes in vivo

Murine cytomegalovirus (MCMV) glycoprotein (gp40) encoded by the m152 gene blocks export of MHC class I complexes from the ERGIC/cis-Golgi compartment, and thereby prevents the presentation of viral antigens to cytotoxic T lymphocytes (Ziegler H., R. Thale, P. Lučin, W. Muranyi, T. Flohr, H. Hengel, H. Farrell, W. Rawlinson, and U.H. Koszinowski. 1997. Immunity 6:57). A recombinant MCMV strain harboring deletion of the m152 gene and the corresponding revertant virus were constructed to investigate the biological significance of this gene product in vivo. Recombinant viruses were selected on the basis of lacZ and/or gpt gene expression and marker genes were subsequently deleted using the cre-loxP recombination system. Deletion of the m152 gene had no effect on virus growth in primary and NIH 3T3 fibroblasts cell culture. The m152 deletion mutant virus replicated to lower titers and exhibited an attenuated disease course in vivo. Depletion studies demonstrated that the absence of m152 gene product renders the virus more sensitive to control by T cells during infection, thus confirming the putative role of this gene product in immunoevasion. In further support of the role of the m152 gene product in evasion of host T-dependent control mechanisms, we report that the deletion mutant and revertant virus strain replicated to similar titers in CD8-knockout mice and in mice deficient of MHC class I molecules. Adoptive transfer studies of naive T lymphocytes also indicated that absence of m152 gene function sensitizes the virus to the primary immune response. Altogether, the results demonstrated that expression of a single viral glycoprotein that interferes with the process of antigen presentation in contex of MHC class I pathway strongly modulates the function of T lymphocytes in vivo.

cytomegalovirus; m152 gene; T lymphocytes

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