The Adenovirus E3 Promoter Is Sensitive to Activation Signals in Human T Cells

Abstract

). This finding suggests that immune evasion strategies of human adenoviruses may be directed, in part, toward protection of persistently or latently infected T lymphocytes. Many of the adenoviral gene products implicated in prevention of immune destruction of virus-infected cells are encoded within the E3 transcription unit. In this study, the E3 promoter was evaluated for sensitivity to T-cell activation signals by using a promoter reporter plasmid. Indeed, this promoter is extremely sensitive to T-cell activation, with phorbol myristate acetate (PMA) plus ionomycin increasing E3-directed transcription 100-fold. By comparison, in the same cells E1A expression leads to a 5.5-fold increase in transcription from the E3 promoter. In contrast to induction by E1A, activation by PMA plus ionomycin requires the two E3 NF-B binding sites. Interestingly, expression of E1A inhibits induction of the E3 promoter in response to T-cell activation while increasing E3 promoter activity in unactivated cells. Collectively, these data suggest that the E3 promoter may have evolved the capacity to respond to T-cell activation in the absence of E1A expression and may act to upregulate antiapoptotic gene expression in order to promote survival of persistently infected T lymphocytes.

Adenovirus Death Protein (ADP) Is Required for Lytic Infection of Human Lymphocytes

“…Although delayed expression of both early and late genes was seen among infected lymphocytes by McNees et al, the selective reduction of a single viral gene over other viral genes was not observed, making the regulation of ADP expression in lymphocytes unique among the adenoviral genes thus evaluated. It was noted that certain adenoviral gene promoters are sensitive to T-cell activation signals (44). It will be interesting to see if these activation signals also affect ADP expression at the level of transcription or at a posttranscriptional step during reactivation of persistently infected cells.…”

Latent Species C Adenoviruses in Human Tonsil Tissues

“…Furthermore, like all DNA viruses that form latent or persistent infections (21), human species C adenoviruses encode a variety of gene products, primarily within the E3 transcription unit, that function to counteract host antiviral defense mechanisms (36). We have previously reported that the E3 promoter is upregulated when cells are exposed to signals that activate T lymphocytes (39). Hence, it appears likely that the immune evasion strategies of these viruses are directed toward protecting the T lymphocyte from destruction during the period of viral activation from latency.…”

E4orf3 Is Necessary for Enhanced S-Phase Replication of Cell Cycle-Restricted Subgroup C Adenoviruses

“…Recently, Garnett and associates recovered group C Ad from mucosal T lymphocytes of children (4). Studying the regulation of the E1A and E3 promoter in T-cell lines, Mahr et al have suggested that upregulation of the E3 promoter may occur in activated T cells in an E1A-independent manner (10). Because the E1B promoter depends strongly on E1A for activation (3), a virus that reactivates in the absence of E1A expression may express little if any E1B-55K.…”