Inducible nitric oxide synthase expression inhibition by adenovirus E1A.
Nitric oxide (NO) is an antiviral effector of the innate immune system. Viruses that can interfere with NO synthesis may be able to replicate more rapidly than viruses that cannot limit NO synthesis. We show that the adenovirus E1A protein inhibits NO production by decreasing expression of the inducible NO synthase (NOS2). The amino-terminal portion of E1A decreases transactivation of the NOS2 5'-flanking region, limiting the DNA binding activity of NF-kappaB and inhibiting NOS2 expression. E1A is thus able to deactivate a critical component of the host defense against viral infection. Viral inhibition of NO production is a mechanism that may enable certain viruses to evade the host innate immune system.
Cao
Wangsen
W
Division of Cardiology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. wcao1@jhmi.edu
Bao
Clare
C
Lowenstein
Charles J
CJ
D000123:Acetyltransferases / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D016328:NF-kappa B; D029701:Saccharomyces cerevisiae Proteins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D004247:DNA; D007372:Interferons; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000123:Acetyltransferases; D051548:Histone Acetyltransferases