Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

NLR Family, Pyrin Domain-Containing 3 Protein*/metabolism ; Infectious Anemia Virus, Equine*/immunology ; Infectious Anemia Virus, Equine*/genetics ; NIMA-Related Kinases*/metabolism ; Viral Vaccines*/immunology ; Viral Envelope Proteins*/immunology ; Viral Envelope Proteins*/metabolism ; Viral Envelope Proteins*/genetics; Animals ; Humans ; Horses ; HEK293 Cells ; Interleukin-1beta/metabolism

Competing Interests: The authors have declared that no competing interests exist.
The current equine infectious anemia virus (EIAV) vaccine causes attenuation of the inflammatory response to an appropriate level, compared to that produced by virulent EIAV. However, how the EIAV vaccine finely regulates the inflammatory response remains unclear. Using a constructed NLRP3-IL-1β screening system, viral proteins from two EIAV strains (the attenuated vaccine and its virulent mother strain) were examined separately. Firstly, EIAV-Env was screened to direct binding P2X7 (R) with notable K+ efflux trans-cellularly. Secondly, EIAV-Env was found to bind NLRP3 and/or NEK7 to trigger aggregation of NLRP3-NEK7 to form NLRP3-NEK7 complex in cells. Comparison of the two strains, we observed a significant reduction on vaccine-Env-initiated NLRP3-NEK7 complex formation, with no difference in Env triggering P2X7 (R)-mediated ion fluxes. Thirdly, reciprocally mutation on four stable varied amino acids between two strains produced an anticipated outcome on NLRP3-IL-1β-axis activation. As the attenuated vaccine was shown evolved as a natural quasispecies of the virulent EIAV, its precise and adaptable regulation via spatial proximity-dependent intracellular activation might present a "win-win" virus-host adaption, offering an alternative strategy on envelop-based vaccines development.
(Copyright: © 2025 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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0 (NLR Family, Pyrin Domain-Containing 3 Protein)
EC 2.7.11.1 (NIMA-Related Kinases)
0 (Viral Vaccines)
0 (Viral Envelope Proteins)
0 (Interleukin-1beta)

Date Created: 20250616 Date Completed: 20250624 Latest Revision: 20250626

20250626

PMC12187018

10.1371/journal.ppat.1012772

40522989