Abstract
Interferons constitute the earliest immune response against viral
infection. They elicit antiviral effects as well as multiple
biological responses involved in cell growth regulation and immune
activation. Because the interferon-induced cellular antiviral response
is the primary defense mechanism against viral infection, many viruses
have evolved strategies to antagonize the inhibitory effects of
interferon. Here, we demonstrate a strategy that Kaposi's
sarcoma-associated herpesvirus uses to block virus-mediated induction
of type I interferon. We found that a viral immediate-early protein,
namely ORF45, interacts with cellular interferon-regulatory factor 7
(IRF-7). In consequence, IRF-7 phosphorylation is inhibited and the
accumulation of IRF-7 in the nucleus in response to viral infection is
blocked. IRF-7 is a transcription regulator that is responsible for
virus-mediated activation of type I interferon genes. By blocking the
phosphorylation and nuclear translocation of IRF-7, ORF45 efficiently
inhibits the activation of interferon α and β genes during viral
infection. Inhibition of interferon gene expression through a viral
protein blocking the activation and nuclear translocation of a crucial
transcription factor is a novel mechanism for viral immune
evasion.