Kaposi's Sarcoma-associated Herpesvirus Latent Gene VFLIP Inhibits Viral Lytic Replication Through NF-kappaB-mediated Suppression of the AP-1 Pathway: a Novel Mechanism of Virus Control of Latency

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2008 Feb 29

PMID 18305042

Citations 69

Authors

Feng-Chun Ye

Fu-Chun Zhou

Jian-Ping Xie

Tao Kang

Whitney Greene

Kurt Kuhne

Xiu-Fen Lei

Qui-Hua Li

Shou-Jiang Gao

Affiliations

Soon will be listed here.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) latency is central to the evasion of host immune surveillances and induction of KSHV-related malignancies. The mechanism of KSHV latency remains unclear. Here, we show that the KSHV latent gene vFLIP promotes viral latency by inhibiting viral lytic replication. vFLIP suppresses the AP-1 pathway, which is essential for KSHV lytic replication, by activating the NF-kappaB pathway. Thus, by manipulating two convergent cellular pathways, vFLIP regulates both cell survival and KSHV lytic replication to promote viral latency. These results also indicate that the effect of the NF-kappaB pathway on KSHV replication is determined by the status of the AP-1 pathway and hence provide a mechanistic explanation for the contradictory role of the NF-kappaB pathway in KSHV replication. Since the NF-kappaB pathway is commonly activated during infection of gammaherpesviruses, these findings might have general implications for the control of gammaherpesviral latency.

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