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同源或异源非洲猪瘟病毒感染后免疫猪单核细胞中基因表达的分析。

Analysis of gene expression in monocytes of immunized pigs after infection with homologous or heterologous African swine fever virus.

作者信息

Kholod Natalia, Koltsov Andrey, Koltsova Galina

机构信息

Laboratory of Viral Genomics, Federal Research Center for Virology and Microbiology, Pokrov, Russia.

出版信息

Front Vet Sci. 2022 Aug 12;9:936978. doi: 10.3389/fvets.2022.936978. eCollection 2022.

Abstract

African swine fever is a deadly disease of pigs caused by the large DNA virus (ASFV). Despite intensive research, little is known about the molecular mechanisms of ASFV pathogenesis. Transcriptome analysis of host and viral genes in infected macrophages revealed changes in expression of genes involved in various biological processes, including immune response, inflammatory response and apoptosis. To understand the mechanisms of virus pathogenesis, we used transcriptome analysis to identify the differences in gene expression between peripheral blood monocytes (PBMCs) isolated from pigs immunized with attenuated Congo ASFV strain (KK262), and then infected with virulent homologous Congo strain (K49) or heterologous Mozambique strain (M78). We found that overexpression of IFN-γ was detected only in cells infected with M78, although the expression of interferon-stimulated genes was increased in both types of cells. In addition, up-regulation of pro-inflammatory cytokines and chemokines was found in PBMCs infected with the heterologous strain M78, in contrast to the cells infected with K49. These data may indicate the beginning of an early immune response in cells infected with a heterologous, but not homologous strain. Transcriptome analysis revealed down-regulation of genes involved in endocytosis and phagocytosis in cells infected with the K49 strain, but not in PBMCs infected with M78. On the contrary, we detected activation of endoplasmic reticulum stress response genes in cells infected with a homologous strain, but not in cells infected with a heterologous strain. This study is the first attempt to determine the differences in the response to ASF infection between homologous and heterologous strains at the cellular level. Our results showed that not only genes of the immune response, but also genes involved in endocytosis and cellular stress response may be important for the formation of cross-protective immunity. This data may be useful for vaccine development or testing of candidate vaccines.

摘要

非洲猪瘟是由大型DNA病毒(非洲猪瘟病毒)引起的猪的致命疾病。尽管进行了深入研究,但对非洲猪瘟病毒发病机制的分子机制了解甚少。对感染巨噬细胞中的宿主和病毒基因进行转录组分析,揭示了参与各种生物学过程(包括免疫反应、炎症反应和细胞凋亡)的基因表达变化。为了解病毒发病机制,我们利用转录组分析来确定从用减毒刚果非洲猪瘟病毒株(KK262)免疫的猪中分离出的外周血单核细胞(PBMC),然后用强毒同源刚果株(K49)或异源莫桑比克株(M78)感染后基因表达的差异。我们发现,仅在感染M78的细胞中检测到IFN-γ的过表达,尽管两种类型的细胞中干扰素刺激基因的表达均增加。此外,与感染K49的细胞相比,在感染异源株M78的PBMC中发现促炎细胞因子和趋化因子上调。这些数据可能表明感染异源而非同源株的细胞中早期免疫反应的开始。转录组分析显示,感染K49株的细胞中参与内吞作用和吞噬作用的基因下调,但感染M78的PBMC中未下调。相反,我们在感染同源株的细胞中检测到内质网应激反应基因的激活,但在感染异源株的细胞中未检测到。本研究首次尝试在细胞水平上确定同源株和异源株对非洲猪瘟感染反应的差异。我们的结果表明,不仅免疫反应基因,而且参与内吞作用和细胞应激反应的基因对于交叉保护性免疫的形成可能也很重要。这些数据可能对疫苗开发或候选疫苗测试有用。

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