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Mutations in feline infectious peritonitis virus nonstructural protein 14/16 methyltransferase attenuate the pathogenicity of the virus in cats

  • 0National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Journal of Virology +

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September 9, 2025

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September 9, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Mutating methyltransferase (MTase) enzymes in feline infectious peritonitis virus (FIPV) nonstructural proteins nsp14 and nsp16 created less pathogenic strains. The dnsp14 mutant demonstrated reduced virulence, induced a stronger immune response, and offered partial protection in cats, suggesting potential as a vaccine candidate.

Area Of Science

  • Veterinary Virology
  • Immunology
  • Molecular Biology

Background

  • Feline infectious peritonitis virus (FIPV) causes a fatal immune-mediated disease in cats.
  • Current vaccines offer limited clinical protection against FIPV.
  • The methyltransferase (MTase) activity of FIPV nonstructural proteins nsp14 and nsp16 is linked to virulence, but its mutation effects are unstudied.

Purpose Of The Study

  • To investigate the impact of nsp14 and nsp16 methyltransferase active site mutations on FIPV virulence and immunogenicity.
  • To develop a less pathogenic FIPV strain for potential vaccine development.

Main Methods

  • Rescued two mutant FIPV strains (dnsp14, dnsp16) by mutating nsp14 (N415) and nsp16 (D129) MTase active sites.
  • Assessed <i>in vitro</i> syncytium formation and growth kinetics.
  • Evaluated <i>in vivo</i> pathogenicity, immune response (interferon, cytokines, neutralizing antibodies), and protective efficacy in cats.

Main Results

  • dnsp14 and dnsp16 showed similar <i>in vitro</i> replication as wild-type FIPV and increased interferon/cytokine expression.
  • Both mutants exhibited significantly reduced pathogenicity in cats, lowering mortality by 75%.
  • dnsp14 induced high neutralizing antibody titers and provided 50% protection; dnsp16 induced low titers and failed to protect.

Conclusions

  • Mutations in nsp14 and nsp16 MTase active sites reduce FIPV pathogenicity in cats.
  • dnsp14 is a promising candidate for a live attenuated FIPV vaccine due to its reduced virulence and ability to elicit a protective immune response.
  • Targeting nsp14/nsp16 MTase activity offers a viable strategy for developing FIPV vaccines.

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