Inhibition of Chemokine Expression by Adenovirus Early Region Three (E3) Genes
AUTOR(ES)
Lesokhin, Alexander M.
FONTE
American Society for Microbiology
RESUMO
Adenoviruses (Ad) have a variety of immunoregulatory genes, many of which are clustered in a 3.5-kb segment of DNA known as early region 3 (E3). Ad E3 codes for proteins that downregulate surface expression of class I major histocompatibility antigens and also inhibit tumor necrosis factor alpha (TNF-α)- and Fas-induced cytolysis. We were interested in determining whether chemokine production or activity might also be inhibited by Ad E3 and we have studied this function in a human astrocytoma cell line, U373. Astrocytes constitute a part of the blood-brain barrier, and chemokines (IP-10, IL-8, MCP-1-4, and MIPs) expressed by them may contribute to leukocyte infiltration within the brain during inflammation. When U373 cells are activated by the proinflammatory molecule TNF-α, the increase in chemokine MCP-1, IL-8, and IP-10 transcripts is blocked by a recombinant Ad expressing the E3 genes under cytomegalovirus promoter control. Comparable Ads expressing green fluorescent protein in place of E3 have no effect on these chemokines. Ads also have been extensively studied as gene therapy vectors and most have a deletion of the E3 region to permit the insertion of larger fragments of foreign DNA. Our results suggest that construction of Ad vectors to include E3 expression cassettes will improve the efficacy and safety of such viral-based gene therapy protocols.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=155150Documentos Relacionados
- Role of early region 3 (E3) in pathogenesis of adenovirus disease.
- Redundant control of adenovirus late gene expression by early region 4.
- Adenovirus 2 early region 1A stimulates expression of both viral and cellular genes.
- Genetic organization, size, and complete sequence of early region 3 genes of human adenovirus type 41.
- Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs.