Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor

M Li, H Lee, J Guo, F Neipel, B Fleckenstein… - Journal of …, 1998 - Am Soc Microbiol
M Li, H Lee, J Guo, F Neipel, B Fleckenstein, K Ozato, JU Jung
Journal of virology, 1998Am Soc Microbiol
Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities. The K9
open reading frame of Kaposi's sarcoma-associated herpesvirus (KSHV) exhibits significant
homology with cellular IFN regulatory factors (IRFs). We have investigated the functional
consequence of K9 expression in IFN-mediated signal transduction. Expression of K9
dramatically repressed transcriptional activation induced by IFN-α,-β, and-γ. Further, it
induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation …
Abstract
Interferons (IFNs) are a family of multifunctional cytokines with antiviral activities. The K9 open reading frame of Kaposi’s sarcoma-associated herpesvirus (KSHV) exhibits significant homology with cellular IFN regulatory factors (IRFs). We have investigated the functional consequence of K9 expression in IFN-mediated signal transduction. Expression of K9 dramatically repressed transcriptional activation induced by IFN-α, -β, and -γ. Further, it induced transformation of NIH 3T3 cells, resulting in morphologic changes, focus formation, and growth in reduced-serum conditions. The expression of antisense K9 in KSHV-infected BCBL-1 cells consistently increased IFN-mediated transcriptional activation but drastically decreased the expression of certain KSHV genes. Thus, the K9 gene of KSHV encodes the first virus-encoded IRF (v-IRF) which functions as a repressor for cellular IFN-mediated signal transduction. In addition, v-IRF likely plays an important role in regulating KSHV gene expression. These results suggest that KSHV employs an unique mechanism to antagonize IFN-mediated antiviral activity by harboring a functional v-IRF.
American Society for Microbiology