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Divergence in poxvirus-encoded E3-like proteins can dictate poxvirus activation of cellular necroptosis - PubMed

4 hours ago
  • #E3-like proteins
  • #poxvirus
  • #necroptosis
  • Poxvirus-encoded E3-like proteins regulate cellular antiviral responses and contain two domains: N-terminal Zα-BD and C-terminal dsRNA-BD.
  • Homology modeling identified dsRNA-BD-fold proteins in most poxviruses except avipoxviruses, salmon poxvirus, and entomopoxviruses, with acquisition events classifying them into three categories.
  • The Zα-BD, involved in necroptosis inhibition, is absent in some poxviruses like leporipoxvirus, leading to RIPK1/RIPK3-mediated necroptosis activation in competent cells.
  • Leporipoxviruses lack necroptosis countermeasures, possibly due to no selective pressure in lagomorph hosts, unlike orthopoxviruses that inhibit necroptosis with Zα-BD.
  • E3-like protein evolution shows structural conservation in dsRNA-BD but diversity in Zα-BD, highlighting host selective pressure shaping viral divergence and immune evasion.