IBENS, Department of Biology, Ecole Normale Supérieure, CNRS, Inserm, PSL Research University, Paris, France.
Institut Pasteur, Université Paris Cité, Unité des Bactéries pathogènes entériques Paris, Paris, France.
PLoS Pathog. 2024 Jun 11;20(6):e1012259. doi: 10.1371/journal.ppat.1012259. eCollection 2024 Jun.
Antagonistic relationships such as host-virus interactions potentially lead to rapid evolution and specificity in interactions. The Orsay virus is so far the only horizontal virus naturally infecting the nematode C. elegans. In contrast, several related RNA viruses infect its congener C. briggsae, including Santeuil (SANTV) and Le Blanc (LEBV) viruses. Here we focus on the host's intraspecific variation in sensitivity to these two intestinal viruses. Many temperate-origin C. briggsae strains, including JU1264 and JU1498, are sensitive to both, while many tropical strains, such as AF16, are resistant to both. Interestingly, some C. briggsae strains exhibit a specific resistance, such as the HK104 strain, specifically resistant to LEBV. The viral sensitivity pattern matches the strains' geographic and genomic relationships. The heavily infected strains mount a seemingly normal small RNA response that is insufficient to suppress viral infection, while the resistant strains show no small RNA response, suggesting an early block in viral entry or replication. We use a genetic approach from the host side to map genomic regions participating in viral resistance polymorphisms. Using Advanced Intercrossed Recombinant Inbred Lines (RILs) between virus-resistant AF16 and SANTV-sensitive HK104, we detect Quantitative Trait Loci (QTLs) on chromosomes IV and III. Building RILs between virus-sensitive JU1498 and LEBV-resistant HK104 followed by bulk segregant analysis, we identify a chromosome II QTL. In both cases, further introgressions of the regions confirmed the QTLs. This diversity provides an avenue for studying virus entry, replication, and exit mechanisms, as well as host-virus specificity and the host response to a specific virus infection.
拮抗关系,如宿主-病毒相互作用,可能导致相互作用的快速进化和特异性。到目前为止,Orsay 病毒是唯一一种自然感染线虫 C. elegans 的水平病毒。相比之下,有几种相关的 RNA 病毒感染其近缘种 C. briggsae,包括 Santeuil(SANTV)和 Le Blanc(LEBV)病毒。在这里,我们专注于宿主对这两种肠道病毒的种内敏感性变化。许多来源于温带的 C. briggsae 菌株,包括 JU1264 和 JU1498,对两者都敏感,而许多热带菌株,如 AF16,则对两者都有抗性。有趣的是,一些 C. briggsae 菌株表现出特定的抗性,如 HK104 菌株,对 LEBV 具有特异性抗性。病毒敏感性模式与菌株的地理和基因组关系相匹配。受严重感染的菌株会产生看似正常的小 RNA 反应,但不足以抑制病毒感染,而抗性菌株则没有小 RNA 反应,这表明病毒进入或复制受到早期阻断。我们从宿主方面采用遗传方法来绘制参与病毒抗性多态性的基因组区域。利用对病毒有抗性的 AF16 和 SANTV 敏感的 HK104 之间的高级交叉重组近交系(RILs),我们在染色体 IV 和 III 上检测到数量性状基因座(QTLs)。在病毒敏感的 JU1498 和 LEBV 抗性的 HK104 之间构建 RILs,然后进行 bulk segregant analysis,我们确定了一个染色体 II QTL。在这两种情况下,进一步对这些区域进行基因导入证实了 QTLs 的存在。这种多样性为研究病毒进入、复制和退出机制以及宿主-病毒特异性和宿主对特定病毒感染的反应提供了途径。