题目:PRRS控制和清除策略

简介:

1994年,随着PRRSV弱毒疫苗(MLV)的供应,首次出现了控制PRRS的方法。然而,PRRSV弱毒疫苗并未完全达到预期,且存在一些缺陷:不完全保护、疫苗毒散毒、持续感染、无法区分受感染猪只和免疫猪只以及毒力返强等。

新技术正在出现,有助于疾病控制并有助于新的疫苗设计和开发。本期主要介绍PRRSV的背景知识、检测方法和防治策略,包括分子生物学、免疫学和遗传学等方面的内容。

概述:

现场控制PRRS的一个重要工具是诊断检测。在分子水平上,应用下一代测序(NGS)为全基因组测序创造了机会,取代了传统的ORF5测序,用于识别病毒分离株。定量描述PRRS病毒的多样性(种属、亚型、分离株、变异株等)对了解PRRSV毒力、细胞趋向性、免疫发病机制、疫苗设计、流行病学和诊断至关重要。 Cortey指出 下一代测序 (NGS) 对 PRRSV序列 进行 更深入的研究,从而改进PRRSV分子流行病学分析。

另一个方面是开发和应用低成本监测工具。Rotolo等人调查了猪场口腔液采样指南,该指南通过RT-PCR检测口腔液中PRRSV病毒水平。HP PRRSV特征:组织趋向性扩大、诱导细胞凋亡的能力增强、异常的炎症细胞因子反应、易受细菌感染和细菌感染增强发病机制、宿主免疫失调,PRRSV RNA聚合酶易出错的特性导致病毒进化,一个重要的结果是毒力增强以及现有疫苗缺乏交叉保护。

总结:

最后,再次声明,我们对PRRS的认识还存在许多空白。除了开展更有效疫苗的研究外,我们对PRRS的认识仍存在许多空白,如表1所示。

表1:当前控制和消除PRRS的研究空白

注释:

①Viral Diversity:关于病毒多样性的认识

Complete sequence of viral genomes is limited:病毒全基因组测序是有限的

Incomplete knowledge of true causes of viral virulence:对病毒真正导致发病原因未完全了解

Robust methods for full viral sequencing are just being developed:稳定的全基因组测序方法正在开发中

Verification of genome elements that contribute to the different pathothypes:验证基因组会导致不同病理类型

Improved diagnostics are needed:需要改进诊断方法

Ability to verify pathotype within hours:能在数小时内确认病理类型

②Viral Receptor:病毒受体

Identification of macrophage receptor protein that interacts with GP5:确定巨噬细胞受体蛋白与GP5相互作用

Alternate target for anti-virals:选择抗病毒药物的靶点

Identification of exact epitopes of GP2/3/4 heterotrimer that interact with macrophage CD163:确定GP2/3/4异三聚体准确表位与巨噬细胞CD163相互作用

Improved targets for vaccine and anti-viral design:改进疫苗和抗病毒设计的靶点

Identification of epithelial receptor for HP PRRS:确定HP PRRS囊膜受体

Understanding of alternate PRRSV infection pathways; control

of HP PRRS:认识PRRSV感染途径;控制HP PRRS

Certain type 1 PRRSV may not use CD163 as their receptor:PRRSV 1型可能不使用CD163作为受体

Identification of alternative PRRSV infection pathways:确定PRRSV替代感染途径

③Viral replication:病毒复制

Characterization of antigenic targets that allow PRRSV to escape the immune system:允许PRRSV逃逸免疫系统的抗原靶点特性

Prevention of rebound in replication; identification of critical PRRSV control points:防止重新复制;识别关键PRRSV控制点

Verification of unique mechanisms used by HP PRRS to promote replication and viral virulence:验证HP PRRS促进复制和病毒毒力增强的独特机制

Control of spread of HP PRRS:控制HP PRRS的传播

Understand mechanisms that promote genetic diversity and recombination:理解促进遗传多样性和重组的机制

Prevention of new PRRSV variants in the field:预防PRRSV变异

Identification of mechanistic basis for persistence:确定稳定性的机制基础

Decreased threat of PRRS reactivation:降低PRRS重新激活的威胁

Understand mechanisms regulating reproductive failure with-PRRSV infections:了解PRRS感染复制失败的调节机制

Prevention of reproductive PRRS:预防PRRS复制

④Host immunity:宿主免疫方面

Identification of broadly neutralizing antibody epitopes:确定广泛中和抗体表位

Vaccines that protect against wider range of PRRSV isolates:疫苗保护对抗大多数PRRSV分离株

Identification of CD4, CD8T cell epitopes:确定CD4, CD8T细胞表位

Verification of protective, pathologic, and regulatory immune response pathways:保护性、病理性和调节性免疫反应途径的验证

Verification of protective cellular immune pathways, i.e. the contributions of innate,humoral and cellular immune components:保护性细胞免疫途径验证,即先天性、体液和细胞免疫成分的贡献

Improved targets for vaccine and drug development:改进疫苗和药物的开发

Mechanism of virus evasion of immune response is complex:病毒免疫反应逃逸的机制是复杂的

Determination of alternate mechanisms to control viral replication:确定控制病毒复制的替代机制

Verification of mechanism of PRRSV transport from gilt to her fetuses:验证PRRSV从母猪向胎儿传播机制

Alternate control mechanisms for reproductive PRRS:PRRS复制的控制机制

Diverse PRRSVs differentially induce aberrant inflammatory responses:不同PRRSV诱导炎症反应的差异

Definition of alternative targets for anti-virals:确定抗病毒药物的靶点

⑤Host genetics:宿主遗传学

Identification of alternate host genes that contribute to viral pathogenesis or protection:确定宿主基因选择有助于病毒发病机理或预防

Alternative targets for breeders to select for improved host resistance/susceptibility:育种时可以选择靶点来提高宿主的抗性/敏感性

Identification of genes enabling certain fetuses to be more resistant to infection:确定某些胎儿对感染更有抵抗力的基因

Selection of breeders with defined PRRS resistance genotypes:具有特定PRRS抗性基因型的育种品种的选择

Older pigs exhibit resistance to PRRSV infection:年龄较大的猪表现出对PRRSV感染的抵抗力

Identification of age related pathways for new targets for PRRS control:确定控制PRRS与年龄相关通路的新靶点

Certain porcine macrophages are more permissive for PRRSV infection:某些猪巨噬细胞更容易感染PRRSV

Identification of genes/pathways that enhance PRRSV infectivity:确定提高PRRSV感染性的基因/途径

⑥Microbiome:微生物组

Unknown interactions of microbiome with virome in multiple tissue locations:在多个组织微生物与病毒的相互作用未知

Understanding of complexity of factors regulating viral replication:理解调节病毒复制因子的复杂性

Effect of components of microbiome on viral replication, pathogenesis:微生物组成分对病毒复制及发病机制的影响

Alter pig clinical disease; identify targets for improved resistance:改变猪临床疾病;确定提高抵抗力的目标

Effect of prebiotics and probiotics on microbiome and virome:益生元和益生菌对微生物群和病毒的影响

Improve disease prevention and protection:加强疾病预防和保护

事实证明,充分认识和了解蓝耳病任重而道远!