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

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

Publication date: Sep 09, 2025

Feline infectious peritonitis virus (FIPV) can cause an immune-mediated disease that is fatal to felines, but there is a lack of clinically effective protection conferred by vaccines. The methyltransferase (MTase) activity of the coronavirus nonstructural proteins nsp14 and nsp16 affects virulence, but there are no studies on the effect of nsp14 and nsp16 mutations affecting enzyme activity on the virulence of FIPV. In this study, we successfully rescued two mutant strains based on the previous infectious clone QS-79, named FIPV QS-79 dnsp14 and dnsp16, by mutating the MTase active sites of nsp14 (N415) and nsp16 (D129). The dnsp14 and dnsp16 exhibited similar syncytium formation ability and growth kinetics as their parental strains in vitro. Moreover, both mutants stimulated increased expression of interferon and cytokines in a macrophage lineage cell line. The dnsp14 and dnsp16 exhibited significantly lower pathogenicity in cats, with a 75% reduction in mortality compared to the wild type. The dnsp14 and dnsp16 were administered to cats at high (10 TCID) and low (10 TCID) doses for immunization purposes. The dnsp14 resulted in the production of high neutralizing antibody titers (>1:156) at both doses, whereas the dnsp16 only induced low neutralizing antibody titers (

Concepts Keywords
Cats 2’-O-methyltransferase
Coronavirus live attenuated vaccine
Methyltransferase N7-methyltransferase
Mutants nsp14
Virulence nsp16

Semantics

Type Source Name
disease IDO protein
disease IDO virulence
disease IDO cell
disease IDO production

Original Article

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