Murine Gamma Herpesvirus 68 Hijacks MAVS and IKK beta to Abrogate NF kappa B Activation and Antiviral Cytokine Production

作者：Dong Xiaonan^*; Feng Pinghui

来源：PLoS Pathogens, 2011, 7(11): e1002336.

DOI：10.1371/journal.ppat.1002336

Upon viral infection, mitochondrial antiviral signaling (MAVS) protein serves as a key adaptor to promote cytokine production. We report here that murine gamma herpesvirus 68 (gamma HV68), a model virus for oncogenic human gamma herpesviruses, subverts cytokine production via the MAVS adaptor. During early infection, gamma HV68 hijacks MAVS and IKK beta to induce the site-specific phosphorylation of RelA, a crucial subunit of the transcriptionally active NF kappa B dimer, which primes RelA for the proteasome-mediated degradation. As such, gamma HV68 efficiently abrogated NF kappa B activation and cytokine gene expression. Conversely, uncoupling RelA degradation from gamma HV68 infection promoted NF kappa B activation and elevated cytokine production. Loss of MAVS increased cytokine production and immune cell infiltration in the lungs of gamma HV68-infected mice. Moreover, exogenous expression of the phosphorylation-and degradation-resistant RelA variant restored gamma HV68-induced cytokine production. Our findings uncover an intricate strategy whereby signaling via the upstream MAVS adaptor is intercepted by a pathogen to nullify the immediate downstream effector, RelA, of the innate immune pathway.

• 出版日期2011-11