THE ACIDIC DOMAIN OF THE HUMAN CYTOMEGALOVIRUS UL37 IMMEDIATE-EARLY GLYCOPROTEIN IS DISPENSABLE FOR ITS TRANSACTIVATING ACTIVITY AND LOCALIZATION BUT IS NOT FOR ITS SYNERGISM

The product of the human cytomegalovirus (HCMV) immediate early (IE) U L37 gene, gpUL37, is predicted to he a type I membrane-bound glycoprot ein. Typically for HCMV IE proteins, gpUL37 transactivates nuclear gen e expression and acts synergistically with other IE proteins. We have initiated mutational analysis of the gpUL37 domains to determine which are required for its transactivating activity. The acidic domain, a f eature notably required for the activity of many nuclear transcription factors, was deleted from gpUL37. Similar to wild-type gpUL37, the mu tant retained a dose responsive transactivating activity in transientl y transfected HeLa cells. Transactivating activity of the mutant was a lso observed in permissive human diploid fibroblasts when it was cotra nsfected with IE1. However, the gpUL37 acidic domain mutant is defecti ve for synergism with another HCMV 1E protein, puss. We found that wil d-type gpUL37 and its acidic domain mutant (Delta aa53-140) are nonnuc lear proteins and are indistinguishable in localization. Confocal micr oscopy of human cell types coexpressing both HCMV IE regulatory protei ns, IE1 and gpUL37, showed gpUL37 does not colocalize with the IE1 nuc lear protein. Taken together, our results establish that gpUL37 is a n onnuclear protein that requires its acidic domain for synergism with p US3 but not for its transactivating activity or its localization. (C) 1996 Academic Pleas, Inc.