Previous studies have found that NOD-like receptor protein 3 (NLRP3) inflammasome activation triggers caspase-1 activation-induced maturation of interleukin (IL)-1β and IL-18, making it important for the development of host defences against RNA viral diseases. The authors were interested in the role of this protein complex in human metapneumovirus (HMPV) disease. They found that the NLRP3 inflammasome plays a detrimental role during HMPV infection, with its inhibition protecting mice from mortality, and reduced weight loss and inflammation, without affecting viral replication. The authors also found that the NLRP3 inflammasome exerts this deleterious effect via the production of IL-1β, with reduced mortality, weight loss and inflammation seen in IL-1β-deficient (IL-1β-/-) mice during HMPV infection. These effects were not found to be different in IL-1β-/- and wild-type mice treated with an NLRP3 inflammasome inhibitor. The production of IL-1β was also inhibited in bone marrow-derived macrophages that were deficient for NLRP3. The authors also found that small hydrophobic protein-deleted recombinant HMPV (HMPV ΔSH) does not activate caspase-1, normally responsible for IL-1β cleavage and maturation. HMPV ΔSH-infected mice had less weight loss, showed no mortality and had reduced inflammation, compared with wild-type HMPV-infected mice. Therefore the activation of the NLRP3 inflammasome is triggered by HMPV SH protein during HMPV infection. Once activated by the HMPV SH protein, the NLRP3 inflammasome promotes the maturation of IL-1β, exacerbating HMPV-induced inflammation. The blockade of IL-1β production by using NLRP3 inflammasome inhibitors may therefore be a potential new therapy for HMPV infection.
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