Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
Viruses. 2024 Feb 12;16(2):282. doi: 10.3390/v16020282.
Canine parvovirus (CPV) is a single-stranded DNA virus that can cause typical hemorrhagic enteritis, and it is one of the common canine lethal viruses. In previous studies, we screened the Food and Drug Administration (FDA)'s drug library and identified nitazoxanide (NTZ), which has anti-CPV capabilities. To investigate the potential antiviral mechanisms, we first reconfirmed the inhibitory effect of NTZ on the CPV by inoculating with different doses and treating for different lengths of time. Then, the differences in the transcription levels between the 0.1%-DMSO-treated virus group and the NTZ-treated virus group were detected using RNA-seq, and a total of 758 differential expression genes (DEGs) were finally identified. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed that these genes are involved in a variety of biological processes and/or signaling pathways, such as cell cycle, mitosis and cell proliferation and differentiation. A protein-protein interaction (PPI) analysis further identified hub genes associated with cell cycle and division among the DEGs. In addition, the expression levels of some of the enriched genes were detected, which were consistent with the high-throughput sequencing results. Moreover, when the cell cycle was regulated with cell cycle checkpoint kinase 1 (Chk1) inhibitor MK-8776 or Prexasertib HCl, both inhibitors inhibited the CPV. In summary, the transcriptome differential analysis results presented in this paper lay the foundation for further research on the molecular mechanism and potential targets of NTZ anti-CPV.
犬细小病毒（CPV）是一种单链 DNA 病毒，可引起典型的出血性肠炎，是常见的犬致命病毒之一。在之前的研究中，我们筛选了美国食品和药物管理局（FDA）的药物库，发现硝唑尼特（NTZ）具有抗 CPV 的能力。为了研究潜在的抗病毒机制，我们首先通过接种不同剂量和不同时间的药物来重新确认 NTZ 对 CPV 的抑制作用。然后，使用 RNA-seq 检测 0.1%-DMSO 处理病毒组和 NTZ 处理病毒组之间的转录水平差异，最终确定了 758 个差异表达基因（DEGs）。进一步对 DEGs 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，这些基因参与了多种生物过程和/或信号通路，如细胞周期、有丝分裂和细胞增殖分化。蛋白质-蛋白质相互作用（PPI）分析进一步确定了 DEGs 中与细胞周期和分裂相关的关键基因。此外，还检测了一些富集基因的表达水平，与高通量测序结果一致。此外，当用细胞周期检查点激酶 1（Chk1）抑制剂 MK-8776 或 Prexasertib HCl 调节细胞周期时，两种抑制剂都抑制了 CPV。综上所述，本文中呈现的转录组差异分析结果为进一步研究 NTZ 抗 CPV 的分子机制和潜在靶点奠定了基础。
