ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India.
ICAR-Indian Agricultural Research Institute, New Delhi, India.
Sci Rep. 2020 Dec 9;10(1):21593. doi: 10.1038/s41598-020-78541-6.
Foot-and-mouth disease (FMD) endangers a large number of livestock populations across the globe being a highly contagious viral infection in wild and domestic cloven-hoofed animals. It adversely affects the socioeconomic status of millions of households. Vaccination has been used to protect animals against FMD virus (FMDV) to some extent but the effectiveness of available vaccines has been decreased due to high genetic variability in the FMDV genome. Another key aspect that the current vaccines are not favored is they do not provide the ability to differentiate between infected and vaccinated animals. Thus, RNA interference (RNAi) being a potential strategy to control virus replication, has opened up a new avenue for controlling the viral transmission. Hence, an attempt has been made here to establish the role of RNAi in therapeutic developments for FMD by computationally identifying (i) microRNA (miRNA) targets in FMDV using target prediction algorithms, (ii) targetable genomic regions in FMDV based on their dissimilarity with the host genome and, (iii) plausible anti-FMDV miRNA-like simulated nucleotide sequences (SNSs). The results revealed 12 mature host miRNAs that have 284 targets in 98 distinct FMDV genomic sequences. Wet-lab validation for anti-FMDV properties of 8 host miRNAs was carried out and all were observed to confer variable magnitude of antiviral effect. In addition, 14 miRBase miRNAs were found with better target accessibility in FMDV than that of Bos taurus. Further, 8 putative targetable regions having sense strand properties of siRNAs were identified on FMDV genes that are highly dissimilar with the host genome. A total of 16 SNSs having > 90% identity with mature miRNAs were also identified that have targets in FMDV genes. The information generated from this study is populated at http://bioinformatics.iasri.res.in/fmdisc/ to cater the needs of biologists, veterinarians and animal scientists working on FMD.
口蹄疫（FMD）是一种高度传染性的病毒感染，会危及全球大量的牲畜群体，影响野生和家养偶蹄类动物。它会对数以百万计的家庭的社会经济地位产生不利影响。疫苗接种在一定程度上被用来保护动物免受 FMD 病毒（FMDV）的侵害，但由于 FMDV 基因组中的高遗传变异性，现有疫苗的有效性已经降低。另一个当前疫苗不受欢迎的关键方面是，它们不能提供区分感染动物和接种疫苗动物的能力。因此，RNA 干扰（RNAi）作为一种控制病毒复制的潜在策略，为控制病毒传播开辟了新途径。因此，这里试图通过计算方法确定 RNAi 在 FMD 治疗开发中的作用，即：（i）使用靶标预测算法在 FMDV 中鉴定 microRNA（miRNA）靶标，（ii）根据与宿主基因组的不相似性，在 FMDV 中鉴定可靶向的基因组区域，以及（iii）合理的抗 FMDV miRNA 样模拟核苷酸序列（SNSs）。结果显示，在 98 个不同的 FMDV 基因组序列中，有 12 个成熟的宿主 miRNA 有 284 个靶标。对 8 个宿主 miRNA 的抗 FMDV 特性进行了湿实验室验证，结果均观察到不同程度的抗病毒作用。此外，在 FMDV 中发现了 14 个 miRBase miRNA，其靶标可及性优于 Bos taurus。此外，在 FMDV 基因上鉴定出了 8 个具有 sense 链 siRNA 性质的潜在可靶向区域，这些区域与宿主基因组高度不同。还鉴定出了 16 个与成熟 miRNA 具有≥90%同一性的 SNS，它们在 FMDV 基因中有靶标。从这项研究中获得的信息已在 http://bioinformatics.iasri.res.in/fmdisc/ 上发布，以满足从事 FMD 研究的生物学家、兽医和动物科学家的需求。
