title: 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.
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.
authors.affiliation: Tumor Virology Program, Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Ye
authors.forename: Fu-Chun
authors.initials: FC
authors.lastname: Zhou
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Xie
authors.forename: Tao
authors.initials: T
authors.lastname: Kang
authors.forename: Whitney
authors.initials: W
authors.lastname: Greene
authors.forename: Kurt
authors.initials: K
authors.lastname: Kuhne
authors.forename: Xiu-Fen
authors.initials: XF
authors.lastname: Lei
authors.forename: Qui-Hua
authors.initials: QH
authors.lastname: Li
authors.forename: Shou-Jiang
authors.initials: SJ
authors.lastname: Gao
mesh_terms: D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*; D017735:Virus Latency / Q000235:genetics*; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D016328:NF-kappa B; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8