Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1.
Tumor necrosis factor alpha (TNF-alpha) is a key mediator of host immune and inflammatory responses and inhibits herpesvirus replication by cytolytic and noncytolytic mechanisms. TNF-alpha effects are primarily mediated through the major TNF-alpha receptor, TNF-R1, which is constitutively expressed in most cell types. Here we show that the Epstein-Barr virus (EBV) immediate-early protein BZLF1 prevents TNF-alpha activation of target genes and TNF-alpha-induced cell death. These effects are mediated by down-regulation of the promoter for TNF-R1. Additionally, we demonstrate that expression of TNF-R1 is downregulated during the EBV lytic replication cycle. Thus, EBV has developed a novel mechanism for evading TNF-alpha antiviral effects during lytic reactivation or primary infection.
Morrison
Thomas E
TE
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Mauser
Amy
A
Klingelhutz
Aloysius
A
Kenney
Shannon C
SC
D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014764:Viral Proteins
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D018124:Receptors, Tumor Necrosis Factor; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins