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Attenuation mechanisms of the P7-P8 live-attenuated cyvirus cyprinidallo2 vaccine potentially involve apoptosis non-inhibition feature: insights into virus pathogenesis
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DOI：10.1099/jgv.0.002227.png)
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Abstract
En 中文
Cyvirus cyprinidallo2 (CyHV-2) is an alloherpesvirus and the causative agent of herpesviral haematopoietic necrosis in goldfish. Whole-genome sequence comparison of the developed live-attenuated vaccine P7-P8 with virulent CyHV-2 strains revealed seven single-nucleotide polymorphisms, five deletions and one inversion in the ORFs, which may be involved in attenuation. A start codon loss in ORF 113, a putative apoptosisinhibition gene, was observed in the mutations. In vitro assays indicated that apoptosisrelated genes were upregulated in cells inoculated with the vaccine or virulent virus compared to uninfected cells. However, the vaccine group showed increased phosphatidylserine externalization and DNA damage, suggesting the apoptosisinducing properties of P7-P8. In the in vivo experiment, histopathology demonstrated that vaccinated goldfish exhibited immune responses, such as leucocyte aggregation and melanomacrophage centre formation, without marked degeneration. Gene expression analysis showed upregulation of proinflammatory and granzyme B genes in vaccinated fish. In addition, the vaccine strain triggered apoptosis of the infected cells during the early stage of infection, potentially promoting virus clearance and preventing excessive virus replication. The results show that the P7-P8 potentially induces apoptosis and immune responses, contributing to low virus propagation without tissue damage. This study provides insights into CyHV-2 pathogenesis, suggesting that apoptosisrelated genes can be the targets for vaccine development against alloherpesviruses in aquaculture species.
Keywords:
apoptosis
cyvirus cyprinidallo2
host-virus interaction
live-attenuated vaccine
pathogenesis
whole-genome sequencing
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