NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency

• DOI: 10.1371/journal.ppat.1006350
• Publication Date: 2017-05-01T13:50:38Z
• Authors: Zhe Ma; Sharon E. Hopcraft; Fan Yang; Alex Petrucelli; Haitao Guo; Jenny P-Y Ting; Dirk P. Dittmer; Blossom Damania
• Keywords: Lytic cycle; Kaposi's sarcoma-associated herpesvirus; Primary effusion lymphoma; Virus latency

Kaposi's sarcoma-associated herpesvirus (KSHV) is a that linked to sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV establishes persistent latent infection in the human host. undergoes periods of spontaneous reactivation where it can enter lytic replication phase its lifecycle. During reactivation, host innate immune responses are activated restrict viral replication. Here, we report NLRX1, negative regulator type I interferon response, important for optimal from latency. Depletion NLRX1 either iSLK.219 or BCBL-1 cells significantly suppressed global transcription levels compared control group. Concomitantly, fewer particles were present supernatant depleted cells. Further analysis revealed upon depletion, higher IFNβ observed, which was also associated with transcriptional upregulation JAK/STAT pathway related genes both cell lines. To investigate whether contributes NLRX1's role treated TBK1 inhibitor (BX795) siRNA block production. Upon BX795 treatment, depletion exhibited less inhibitory effects on infectious virion production, suggesting facilitates by negatively regulating responses. Our data suggests plays positive suppressing response during process might serve as potential target restricting transmission.