MURINE CYTOMEGALOVIRUS IE2, AN ACTIVATOR OF GENE-EXPRESSION, IS DISPENSABLE FOR GROWTH AND LATENCY IN MICE

The murine cytomegalovirus alpha (immediate-early) gene product, IE2(3 91aa), a protein that is related to the human cytomegalovirus US22 pro tein family, had previously been shown to be dispensable for viral gro wth in cell culture. In transient assays, however, this protein was fo und to transactivate the murine CMV ie1/ie3 and ie2 promoters, as well as a number of other promoters. Transactivation was mediated via prom oter-proximal elements rather than through elements located upstream i n the enhancer region. This activation predicted that ie2 would play a role in regulating gene expression; however, ie2 mutants did not exhi bit altered growth or latency in the mouse. ie2-deficient viruses reac hed peak titers in spleen, salivary glands, lungs, liver, kidneys, pan creas, peripheral blood leukocytes, and adrenal glands that were compa rable to wild-type virus. When assayed by spleen explant culture, ie2- deficient viruses yielded reactivation levels similar to wild type. Th us, the murine CMV ie2 gene encodes a regulatory protein that is dispe nsable for viral infection of cells in culture as well as for interact ion with tissues in the infected BALB/c mouse. (C) 1995 Academic Press , Inc.