Murine Gamma-Herpesvirus 68 Hijacks MAVS and IKKβ to Initiate Lytic Replication

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Upon viral infection, the mitochondrial antiviral signaling (MAVS)-IKKβ pathway is activated to restrict viral replication. Manipulation of immune signaling events by pathogens has been an outstanding theme of host-pathogen interaction. Here we report that the loss of MAVS or IKKβ impaired the lytic replication of gamma-herpesvirus 68 (γHV68), a model herpesvirus for human Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. γHV68 infection activated IKKβ in a MAVS-dependent manner; however, IKKβ phosphorylated and promoted the transcriptional activation of the γHV68 replication and transcription activator (RTA). Mutational analyses identified IKKβ phosphorylation sites, through which RTA-mediated transcription was increased by IKKβ, within the transactivation domain of RTA. Moreover, the lytic replication of recombinant γHV68 carrying mutations within the IKKβ phosphorylation sites was greatly impaired. These findings support the conclusion that γHV68 hijacks the antiviral MAVS-IKKβ pathway to promote viral transcription and lytic infection, representing an example whereby viral replication is coupled to host immune activation.

Vyšlo v časopise: Murine Gamma-Herpesvirus 68 Hijacks MAVS and IKKβ to Initiate Lytic Replication. PLoS Pathog 6(7): e32767. doi:10.1371/journal.ppat.1001001
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001001

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