Faculty of Science, Sydney School of Veterinary Science, The University of Sydney, Sydney, NSW 2006, Australia.
Faculty of Science, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Viruses. 2021 Oct 9;13(10):2040. doi: 10.3390/v13102040.
Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2'-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC, 0.4-0.6 µM, TI = 21; 2CMC EC, 2.7-5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted.
猫杯状病毒（FCV）可引起上呼吸道疾病（URTD）和散发性强毒力系统性疾病（FCV-VSD）暴发。FCV-VSD 病毒毒力增加的基础尚不完全清楚，且尚未开发出针对 FCV-VSD 的抗病毒药物。我们调查了澳大利亚的三次 FCV-VSD 暴发的临床流行病学和病毒特征，并评估了硝唑尼特（NTZ）、2'-C-甲基胞苷（2CMC）和 NITD-008 对 FCV-VSD 病毒的体外疗效。23 例 FCV-VSD 病例的总死亡率为 39%。宏基因组测序在三次暴发中鉴定了五种遗传上不同的 FCV 谱系，所有谱系似乎都在澳大利亚当地进化。值得注意的是，没有发现明显区分 FCV-URTD 和 FCV-VSD 表型的突变。一株 FCV-URTD 株可能起源于重组事件。对培养病毒衣壳上高变区 E 区的七个氨基酸残基进行分析，不支持这些残基的特性可以可靠地区分两种病理型的观点。在蚀斑减少测定中，所有抗病毒药物在低微摩尔浓度下对 FCV-VSD 均表现出剂量反应抑制；NTZ 的 EC₅₀ 为 0.4-0.6 µM，TI = 21；2CMC 的 EC₅₀ 为 2.7-5.3 µM，TI > 18；NITD-008 的 EC₅₀ 为 0.5 至 0.9 µM，TI > 111。值得进一步研究这些抗病毒药物治疗 FCV-VSD。
