engleski

Immunoevasion by TNF regulation - novel function for MCMV ie1 gene

One of the most famous cytokines, tumor necrosis factor (TNF), shows a vast spectrum of bioactivities influencing majority of cell types. Produced mostly by macrophages, it is considered to be a major mediator of inflammation and cellular immune response. Although infection with several viruses has been shown to induce production of TNF, indicating its importance in successful viral clearance, it seems that not many viruses have learned how to control this potent cytokine. However, considering their reputation as masters of disguise, it does not come as a surprise that both human and murine cytomegaloviruses (MCMV) have developed means to avoid TNF-induced response (caspase dependent and independent apoptosis and expression of TNF-induced genes). Here it is shown that the MCMV ie1 gene product acts as a negative regulator of TNF expression in vitro and in vivo at both transcriptional and translational level, thus revealing yet another immunoevasive strategy employed by MCMV. Mice infected with MCMVdie1 show lower viral titers, but higher levels of TNF when compared to mice infected with MCMVdie1-rev or wt virus and this effect is not strain dependant. NK cell depletion didn’t rescue the virus from its attenuated phenotype, indicating that this immunoevasion strategy is directed mostly at macrophages, which in addition of being the main producers of TNF, are also a major site of viral replication, dissemination and establishment of latency. Interestingly, despite the attenuated phenotype, growth kinetics of MCMVdie1 showed reactivation around 30th day PI in spleen, liver, kidney and, most prominently, in salivary gland.

tnf; immunoevasion; immunoregulation; ie1; mcmv

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