The adenovirus e3 promoter is sensitive to activation signals in human T cells.
The group C adenoviruses typically cause acute respiratory disease in young children. In addition, a persistent phase of infection has been observed in which virus may be shed for years without producing overt pathology. Our laboratory recently reported that group C adenovirus DNA can be found in tonsil and adenoid T lymphocytes from the majority of pediatric donors (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). 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-kappaB 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.
Mahr
Jeffrey A
JA
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Boss
Jeremy M
JM
Gooding
Linda R
LR
D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics; D017503:Adenovirus E3 Proteins / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D017503:Adenovirus E3 Proteins; D017931:DNA Primers; D016328:NF-kappa B; D018808:Transcription Factor AP-1