Combined amino acid mutations in position 67 and 438 in the glycoprotein of infectious hematopoietic necrosis virus can further reduce the pathogenicity

IF 3.9 1区农林科学 Q1 FISHERIES

Aquaculture Pub Date : 2025-10-02 DOI:10.1016/j.aquaculture.2025.743255

Shuaibo Li, Rui Ao, Yulu Ma, Xinjia Lv, Min Liu

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引用次数: 0

Abstract

The outbreak of infectious hematopoietic necrosis (IHN), driven by the severe acute IHN virus (IHNV), poses a significant risk to rainbow trout farming in China. As such, the development of effective vaccines and an understanding of their mechanisms are essential. Our previous research demonstrated that mutations at sites 67 and 438 respectively in the G protein of IHNV could reduce its pathogenicity and enhance the survival rate (SR) of rainbow trout post-infection. In this study, we mutated at both amino acid positions 67 and 438 simultaneously in the G protein of IHNV. The resulting recombinant IHNVs (rIHNVs) exhibited similar growth patterns to the parental strain. Additionally, rIHNV-G₆₇_–₄₃₈ induced reduced apoptosis and lower activity of caspase-3 and caspase-9 compared to other groups in vitro. Rainbow trout vaccinated with rIHNV-G₆₇_–₄₃₈ showed significant protection against IHNV, with a relative percent survival (RPS) of approximately 88.9 %, outperforming other groups. Furthermore, vaccination with rIHNV-G₆₇_–₄₃₈ triggered a notable increase in specific IgM antibodies. Notably, an antiviral immune response was rapidly activated early in the vaccination process, evidenced by the upregulation of IL1β, IFN1, IL8, TNF-α, MX1, and TLR3. The viral genomic load in fish vaccinated with rIHNV-G₆₇_–₄₃₈ was significantly lower compared to the other groups. These findings indicate that this vaccine enhances immune responses while reducing viral virulence, making it a promising candidate for the prevention of IHN outbreaks. Additionally, the study provides new insights into the virulence mechanisms of rhabdoviruses and the development of attenuated vaccines.

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感染性造血坏死病毒糖蛋白67位和438位氨基酸联合突变可进一步降低致病性

由严重急性造血坏死病毒（IHNV）引起的传染性造血坏死（IHN）疫情对中国虹鳟鱼养殖构成重大风险。因此，研制有效疫苗并了解其机制至关重要。我们前期的研究表明，IHNV G蛋白的67和438位点突变可以降低其致病性，提高虹鳟鱼感染后的存活率（SR）。在这项研究中，我们同时突变了IHNV的G蛋白的67和438个氨基酸位置。重组ihnv （rihnv）表现出与亲本菌株相似的生长模式。此外，与其他组相比，rIHNV-G67-438诱导细胞凋亡减少，caspase-3和caspase-9活性降低。虹鳟鱼接种了rIHNV-G67-438疫苗，显示出对IHNV的显著保护作用，相对存活率（RPS）约为88.9%，优于其他组。此外，接种rIHNV-G67-438引发特异性IgM抗体显著增加。值得注意的是，在疫苗接种过程的早期，抗病毒免疫反应被迅速激活，il - 1β、IFN1、il - 8、TNF-α、MX1和TLR3的上调证明了这一点。与其他组相比，接种rIHNV-G67-438的鱼的病毒基因组载量显著降低。这些发现表明，该疫苗增强了免疫反应，同时降低了病毒毒力，使其成为预防IHN暴发的有希望的候选疫苗。此外，该研究为横纹肌病毒的毒力机制和减毒疫苗的开发提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Aquaculture 农林科学-海洋与淡水生物学

CiteScore

8.60

自引率

17.80%

发文量

1246

审稿时长

56 days

期刊介绍： Aquaculture is an international journal for the exploration, improvement and management of all freshwater and marine food resources. It publishes novel and innovative research of world-wide interest on farming of aquatic organisms, which includes finfish, mollusks, crustaceans and aquatic plants for human consumption. Research on ornamentals is not a focus of the Journal. Aquaculture only publishes papers with a clear relevance to improving aquaculture practices or a potential application.