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Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor
1New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Journal of Virology
|June 17, 1998
Summary
Kaposi's sarcoma-associated herpesvirus (KSHV) K9 protein acts as a viral IFN regulatory factor (v-IRF), suppressing cellular antiviral responses. This viral protein interferes with interferon signaling and promotes cell transformation.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Interferons (IFNs) are crucial cytokines for antiviral defense.
- Kaposi's sarcoma-associated herpesvirus (KSHV) possesses a K9 open reading frame homologous to cellular IFN regulatory factors (IRFs).
Purpose of the Study:
- To investigate the functional impact of KSHV K9 expression on IFN-mediated signal transduction.
- To determine if KSHV encodes a functional viral IRF (v-IRF) and its role in viral pathogenesis.
Main Methods:
- Assessing the effect of K9 expression on IFN-alpha, -beta, and -gamma induced transcriptional activation.
- Evaluating NIH 3T3 cell transformation upon K9 expression.
- Analyzing the impact of antisense K9 expression in KSHV-infected cells on IFN signaling and viral gene expression.
Main Results:
- K9 expression significantly repressed IFN-induced transcriptional activation.
- K9 expression induced NIH 3T3 cell transformation, including morphologic changes and growth in low-serum conditions.
- Antisense K9 expression in KSHV-infected cells restored IFN-mediated activation and reduced viral gene expression.
Conclusions:
- The KSHV K9 gene encodes the first identified v-IRF, acting as a repressor of cellular IFN signaling.
- v-IRF plays a critical role in regulating KSHV gene expression and antagonizing host antiviral defenses.
- KSHV utilizes v-IRF to evade the host immune response, highlighting a unique viral immune evasion strategy.