Regulation of NF-kB inhibitor IkBα and viral replication by a KSHV microRNA

Lei, X., Bai, Z., Ye, F., Xie, J., Kim, C., Huang, Y., and Gao, S.

Nat. Cell Biol., 12, 193-199, 2010

Speaker：Siao-Fen Yeh (葉曉芬)                                 Time：15:00~16:00, May 26, 2010

Commentator：Dr. Cheng-Chan, Lu (呂政展老師)    Place：Room 601

Abstract：

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is a human γ-herpesvirus. KSHV causes clinic forms of Kaposi’s sarcoma (KS). Many KSs are chronic diseases except AIDS-related KS, which is aggressive (1). Like other herpesvirus, KSHV has lytic and latent stages. Previous studies showed that a cluster of the microRNAs found in the KSHV latent-infected cells played an important role in controlling viral latency, evasion of the host immune system and induction of tumors (1). To determine the function of microRNAs in viral replication, the authors deleted the cluster of microRNAs (ΔmiRNA), and found that the deletion of microRNAs cluster from KSHV genome enhanced the lytic replication of the virus. ∆miRNAs increased lytic gene RTA and MCP expression, but decreased latent gene LANA, vFLIP and vCyclin expression. They also showed that viral latent gene vFLIP regulated latent replication by activating NF-kB (2). The mechanism that the microRNAs regulate NF-kB activity by controlling the activity of the inhibitor IkBα is different from the mechanism of vFLIP. The authors conducted the computational and microRNA seed mutagenesis analysis to identify the microRNA which targets IkBα transcript. miR-K1 was revealed to rescue NF-kB activity and to reduce viral lytic replication. All together, KSHV encodes miR-K1, which regulates lytic replication by activating NF-kB signal pathway. Furthermore, KSHV microRNAs are important in controlling viral latency and lytic replication by operating host death pathway.

References：

1.          Greene, W. et al. Molecular biology of KSHV in relation to AIDS-associated oncogenesis. Cancer Treat. Res. 133, 69-127 (2007)

2.          Ye, F. C. et al. Kaposi’s sarcoma-associated herpesvirus latent gene vFLIP inhibits viral lytic replication through NF-kB-mediated suppression of the AP-1 pathway: a novel mechanism of virus control of latency. J. Virol. 82, 4235-4249 (2008)