The Epstein-Barr virus SM protein induces STAT1 and interferon-stimulated gene expression.
Viruses utilize numerous mechanisms to counteract the host's immune response. Interferon production is a major component of the host antiviral response. Many viruses, therefore, produce proteins or RNA molecules that inhibit interferon-induced signal transduction pathways and their associated antiviral effects. Surprisingly, some viruses directly induce expression of interferon-induced genes. SM, an early lytic Epstein-Barr virus (EBV) nuclear protein, was found to specifically increase the expression of several genes (interferon-stimulated genes) that are known to be strongly induced by alpha/beta interferons. SM does not directly stimulate alpha/beta interferon secretion but instead induces STAT1, an intermediate step in the interferon signaling pathway. SM is a posttranscriptional activator of gene expression and increases STAT1 mRNA accumulation, particularly that of the functionally distinct STAT1beta splice variant. SM expression in B lymphocytes is associated with decreased cell proliferation but does not decrease cell viability or induce cell cycle arrest. These results indicate that EBV can specifically induce cellular genes that are normally physiological targets of interferon by inducing components of cytokine signaling pathways. Our findings therefore suggest that some aspects of the interferon response may be positively modulated by infecting viruses.
Ruvolo
Vivian
V
University of Florida Shands Cancer Center, University of Florida, Gainesville, Florida 32610-0232, USA.
Navarro
Lorena
L
Sample
Clare E
CE
David
Michael
M
Sung
Seung
S
Swaminathan
Sankar
S
D001402:B-Lymphocytes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C090236:SM protein, Human herpesvirus 4; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; D016899:Interferon-beta