THE IMMEDIATE-EARLY GENES OF HUMAN CYTOMEGALOVIRUS UP-REGULATE TUMOR-NECROSIS-FACTOR-ALPHA GENE-EXPRESSION

Cytomegalovirus (CMV) is an important cause of disease in the immunoco mpromised patient and CMV infection is associated with predominantly m ononuclear inflammatory response. Since products of the CMV immediate early (IE) gene region are potent trans-activators, we used the monocy te cell line THP-1 and a transient transfection assay to determine if these viral proteins upregulate expression of the TNF gene. The IE gen es of CMV upregulated TNF gene activity as judged by increases in prom oter activity, steady state mRNA, and protein production. The presence or absence of the 3' untranslated region of the TNF gene did not affe ct gene expression induced by the IE gene products. These studies sugg est that activation of TNF gene expression by the CMV IE gene products may, in part, account for the inflammatory response associated with C MV infections.