In response to viral infection, cells can initiate programmed cell death (PCD), leading to a reduction in the release of viral progeny. Viruses have therefore evolved specific mechanisms to curb PCD. Cytomegaloviruses (CMVs) are particularly sophisticated manipulators of cellular defenses and are known to encode potent inhibitors of apoptosis and necroptosis. However, a CMV inhibitor of pyroptosis, the third major PCD form, has not been identified. Encoding such an inhibitor should be important for the virus as the three PCD pathways are not separate entities but interconnected pathways. Here we identify the murine CMV M84 protein as an inhibitor of pyroptosis and proinflammatory cytokine release. M84 interacts with the pyrin domain of the inflammasome components AIM2 and ASC to block Caspase-1 activation, release of interleukin 1β (IL-1β) and IL-18, cleavage of Gasdermin D, and pyroptosis of macrophages. Growth attenuation of an M84-deficient MCMV in macrophages was rescued by knockout of either Aim2 or Asc or by treatment with a Caspase-1 inhibitor, and its attenuation in infected mice was partially rescued in Asc knockout mice. These results demonstrate that viral inhibition of the inflammasome-pyroptosis pathway is important to promote viral replication and dissemination in vivo.

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The current Integrated Demand Response (IDR) strategies cannot accurately evaluate the user’s maximum response which ignore the user terminal equipment response model. At the same time, the optimization target of the current IDR strategies is mostly electric energy, and other energy response requirements such as natural gas are not considered. This paper establishes an IDR strategy model based on energy models for different equipment terminals of residential users. And calculate the theoretical maximum response potential value of different users according to the response strategy formulated by different energy response requirements with the GA-SQP hybrid algorithm. The example analyses the user response potential in typical scenarios and time periods. The results verify the effectiveness and feasibility of the proposed method.