Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses
2024

Mammalian Proteins ZAP and KHNYN Limit Avian Viruses

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Author Information

Author(s): Jordan T. Becker, Clayton K. Mickelson, Lauren M. Pross, Autumn E. Sanders, Esther R. Vogt, Frances K. Shepherd, Chloe Wick, Alison J. Barkhymer, Stephanie L. Aron, Elizabeth J. Fay, Reuben S. Harris, Ryan A. Langlois

Primary Institution: University of Minnesota – Twin Cities

Hypothesis

Birds are defective in RNA recognition and restriction pathways, presenting a barrier to emergence in mammals.

Conclusion

Mammalian proteins ZAP and KHNYN can independently restrict CpG-enriched avian viruses, including influenza A virus and Rous sarcoma virus.

Supporting Evidence

  • Human ZAP selectively depletes CpG-enriched viral RNAs.
  • Chicken ZAP does not affect IAV replication.
  • Human ZAP-S and KHNYN independently restricted CpG-enriched IAV.
  • Mammalian ZAP and KHNYN restricted Rous sarcoma virus.
  • Platypus KHNYN restricted multiple viruses.

Takeaway

Some proteins in mammals help stop certain bird viruses from making us sick. This study found that two specific proteins, ZAP and KHNYN, do this job well.

Methodology

The study involved genomic, phylogenetic, and functional analyses using chicken and human cells to test the restriction capabilities of ZAP and KHNYN against various viruses.

Limitations

The study primarily used a common laboratory strain of IAV and relied on overexpression of host restriction factors, which may not fully represent natural conditions.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1101/2024.12.23.629495

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