Effects of G and SH Truncation on the Replication, Virulence, and Immunogenicity of Avian Metapneumovirus

VACCINES(2024)

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摘要
Four mutants varying the length of the G and SH genes, including a G-truncated mutant (Delta G) and three G/SH-truncated mutants (Delta SH/G-1, Delta SH/G-2, and Delta SH/G-3), were generated via serially passaging the avian metapneumovirus strain SNU21004 into the cell lines Vero E6 and DF-1 and into embryonated chicken eggs. The mutant Delta G particles resembled parental virus particles except for the variance in the density of their surface projections. G and G/SH truncation significantly affected the viral replication in chickens' tracheal ring culture and in infected chickens but not in the Vero E6 cells. In experimentally infected chickens, mutant Delta G resulted in the restriction of viral replication and the attenuation of the virulence. The mutants Delta G and Delta SH/G-1 upregulated three interleukins (IL-6, IL-12, and IL-18) and three interferons (IFN alpha, IFN beta, and IFN gamma) in infected chickens. In addition, the expression levels of innate immunity-related genes such as Mda5, Rig-I, and Lgp2, in BALB/c mice were also upregulated when compared to the parental virus. Immunologically, the mutant Delta G induced a strong, delayed humoral immune response, while the mutant Delta SH/G-1 induced no humoral immune response. Our findings indicate the potential of the mutant Delta G but not the mutant Delta SH/G-1 as a live attenuated vaccine candidate.
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关键词
avian metapneumovirus,G and SH truncation,virus replication,attenuation,immunogenicity
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