Human cytomegalovirus late protein encoded by ie2: a trans-activator as well as a repressor of gene expression

In order to study the function of human cytomegalovirus (HCMV) immediate early gene 2 (ie2) (UL122) gene products made at late times during infection, cDNA clones were isolated from an expression library made with 74 h post-infection mRNA. Based on screening of the library, 1% of transcripts in infected cells at this time were ie2 region-specific, and transcripts encoding gamma IE2(338aa), a 40K late gene product, were more abundant than those encoding IE2(579aa), an alpha gene product made throughout infection. As expected, the cDNA capable of directing the expression of gamma IE2(338aa) was derived from a contiguous genomic region within exon 5 of the ie1/ie2 region. The cDNA clones encoding gamma IE2(338aa) and IE2(579aa) were compared for their ability to trans-activate viral and cellular promoters and to repress expression from the ie1/ie2 promoter via the ie2 cis-repression signal. Unexpectedly, gamma IE2(338aa) trans-activated a variety of test promoters when cotransfected with the major alpha gene product, IE1(491aa). Promoters derived from the cellular beta-actin gene, the simian virus 40 early region and the human immunodeficiency virus were all responsive to gamma IE2(338aa) plus IE1(491aa), although several beta promoters derived from the HCMV genome were unresponsive. Thus, this abundant late product from the ie2 region may play a role in trans-activation in addition to its role as a repressor of alpha gene expression.