Convergent loss of the necroptosis pathway in disparate mammalian lineages shapes virus countermeasures

  title={Convergent loss of the necroptosis pathway in disparate mammalian lineages shapes virus countermeasures},
  author={Ana {\'A}gueda-Pinto and Lu{\'i}s Q. Alves and Fabiana Neves and Grant McFadden and Bertram L Jacobs and Luis Filipe C. Castro and Masmudur Rahman and Pedro Jos{\'e} Esteves},
Programmed cell death is a vital process in the life cycle of an organism. Necroptosis, an evolutionary restricted form of programmed necrosis, contributes to the innate immune response by killing pathogen-infected cells. This virus-host interaction pathway is organized around two key components: the receptor-interacting protein kinase 3 (RIPK3), which recruits and phosphorylates the mixed lineage kinase-like protein (MLKL), thus inducing cellular plasma membrane rupture and cell death… 
The evolution of regulated cell death pathways in animals and their evasion by pathogens
The molecular pathways of regulated cell death, their roles in infection, and how they are perturbed by viruses and bacteria are reviewed, providing insights into the coevolution of host-pathogen interactions and cell death pathways.


Necroptosis and its role in infectious diseases
It was found that necroptosis is not only involved in the physiological regulation but also in the occurrence, development and prognosis of some necrotic diseases, especially infectious diseases.
Necroptosis in anti-viral inflammation
Recent advances on how viruses counteract this host defense mechanism and the effect of necroptosis on the anti-viral inflammatory reaction are discussed.
Combined Knockout of RIPK3 and MLKL Reveals Unexpected Outcome in Tissue Injury and Inflammation
It is demonstrated that Ripk3 or Mlkl-deficient mice are protected to a similar extent from kidney ischemia reperfusion injury and TNF-induced toxicity and Paradoxically, the double-knockout mice resembled, in each case, the vulnerable wild-type mice, revealing novel complexities in the mechanisms of inflammation-driven diseases, due to aberrant cell death.
Virus inhibition of RIP3-dependent necrosis.
Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the vaccinia virus innate immune evasion protein, E3
It is demonstrated that the N terminus of the VACV E3 protein prevents DAI-mediated induction of necroptosis, and pathogenicity was restored in either RIPK3- orDAI-deficient mice.
Apoptosis and Necroptosis as Host Defense Strategies to Prevent Viral Infection.