ENHANCER REQUIREMENT FOR MURINE CYTOMEGALOVIRUS GROWTH AND GENETIC COMPLEMENTATION BY THE HUMAN CYTOMEGALOVIRUS ENHANCER

The cytomegalovirus (CMV) enhancer is a highly complex regulatory regi on containing multiple elements that interact with a variety of host-e ncoded transcription factors. Many of these sequence elements are cons erved among the different species strains of CMV, although the arrange ment of the various elements and overall sequence composition of the C MV enhancers differ remarkably. To delineate the importance of this re gion to a productive infection and to explore the possibility of gener ating a murine CR IV (MCMV) under the control of human CMV (HCMTV) gen etic elements, the MCMV enhancer was resected and replaced either with nonregulatory sequences or with paralogous sequences from HCMV. The e ffects of these various deletions and substitutions on viral growth in transfected or infected tissue-culture cells were evaluated, We found that mutations in MCMV that eliminate or substitute for the enhancer with nonregulatory sequences showed a severe deficiency in virus synth esis. This growth defect is effectively complemented by the homologous MCMV enhancer as well as the HCMV enhancer. In the latter case, the c himeric viruses (hybrid MCMV strains) containing the molecularly shuff led human enhancer exhibit infectious kinetics similar to that of pare ntal wild-type and wild-type revertant MCMV. These results also show t hat open reading frames m124, mill. I. and m125 located within the enh ancer legion are nonessential for growth of MCMV in cells. Most import antly, we conclude that the enhancer of MCMV is required for optimal i nfection and that its diverged human counter-part can advantageously r eplace its role in promoting viral infectivity.