基于高通量测序和小分子核苷类似物诊断与治疗猫传染性腹膜炎病例转归

doi:10.11843/j.issn.0366-6964.2022.01.020

畜牧兽医学报 ›› 2022, Vol. 53 ›› Issue (1): 200-208.doi: 10.11843/j.issn.0366-6964.2022.01.020

基于高通量测序和小分子核苷类似物诊断与治疗猫传染性腹膜炎病例转归

李笨¹, 郭富强², 王伟伟¹, 金宁一³, 金秋实⁵, 米志强⁴, 李昌^3*, 王茂鹏^1*

1. 温州大学病毒学研究所, 温州 325035;
2. 瑞鹏宠物医院, 深圳 518000;
3. 中国农业科学院长春兽医研究所, 长春 130122;
4. 军事医学研究院微生物流行病研究所, 北京 100071;
5. 牡丹江心血管病医院影像介入诊疗中心, 牡丹江 157001

收稿日期:2021-04-06 出版日期:2022-01-23 发布日期:2022-01-26
通讯作者: 王茂鹏,主要从事兽医传染病与免疫相关研究,E-mail:wangmaopenga@126.com;李昌,主要从事病毒感染与免疫相关研究,E-mail:lichang78@163.com
作者简介:李笨(1993-),男,辽宁兴城人,硕士,主要从事微生物与免疫研究,E-mail:15524436701@163.com
基金资助:
国家重点研发计划（2017YFF0108605；2018YFC160025）；国家自然科学基金青年基金（31802224）；温州市科技特派员专项（X20210072）

A Case Report of Feline Infectious Peritonitis based on High-throughput Sequencing Diagnosis and Small-molecule Nucleoside Analogues Treatment

LI Ben¹, GUO Fuqiang², WANG Weiwei¹, JIN Ningyi³, JIN Qiushi⁵, MI Zhiqiang⁴, LI Chang^3*, WANG Maopeng^1*

1. Institute of Virology, Wenzhou University, Wenzhou 325035, China;
2. Ruipeng Pet Hospital, Shenzhen 518000, China;
3. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China;
4. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China;
5. Centre of Imaging Diagnosis and Interventional Treatment, Mudanjiang Cardiovascular Disease Hospital of Heilongjiang Province, Mudanjiang 157001, China

Received:2021-04-06 Online:2022-01-23 Published:2022-01-26

摘要/Abstract

摘要： 猫传染性腹膜炎（简称猫传腹）是一类由冠状病毒引起、以严重腹腔炎症为特征的高致死性传染病，然而对其病原的诊断尚无公认的标准方法，且无有效的治疗手段可应用于兽医临床。因此，本研究通过描述一例猫传染性腹膜炎病例诊治过程，探索针对该病的合理诊疗手段。本研究利用高通量测序技术，综合临床症状、生化分析、血常规等检测方法，实现对该病例的诊断，基于白/球蛋白比、fSAA等临床指标评估抗病毒药物GS-441524治疗效果，监控转归进程。结果表明高通量测序技术可应用于猫传腹的诊断过程，经高剂量药物治疗后临床症状明显改善，8周白/球蛋白比、fSAA两项特征指标恢复正常，10周符合出院标准，16周复查未见疾病复发迹象。此病例的成功治疗证明高通量测序技术在兽医临床诊断的应用价值和GS-441524药物对危重病例治疗的有效性，血清白/球蛋白比（≥0.6）和fSAA （<5 μg·mL^-1）可作为临床指标评估治疗效果。

关键词: 猫传染性腹膜炎, 猫冠状病毒, 高通量测序技术, GS-441524

Abstract: Feline infectious peritonitis (FIP) is a highly lethal infectious disease caused by coronavirus and characterized by severe abdominal cavity inflammation. However, there is no approved standard method for the diagnosis or treatment of pathogen. Therefore, this study describes the diagnosis and treatment process from a case report of feline infectious peritonitis and explores reasonable diagnosis and treatment methods for the disease. High-throughput sequencing technology, clinical symptoms, biochemical analysis, blood routine and etc. were comprehensively used to diagnose this case, to evaluate the treatment effect of the antiviral drug GS-441524 with albumin/globulin ratio and fSAA level, and to monitore the sequelae. Results showed that high-throughput sequencing technology can be applied to the diagnosis of FIP. After high-dose drug treatment, the clinical symptoms were significantly improved, the albumin/globulin ratio and fSAA were restored to normal at 8 weeks, and the discharge standards were met at 10 weeks. No signs of disease recurrence were found during the 16-week review. The successful treatment of this case proves the potential of high-throughput sequencing technology in veterinary clinical diagnosis, and the effectiveness of GS-441524 in the treatment of critical cases. The serum albumin/globulin ratio (≥0.6) and fSAA (<5 μg·mL^-1) can be a clinical indicator to evaluate the therapeutic effect.

Key words: feline infectious peritonitis, feline coronavirus, high-throughput sequencing technology, GS-441524

中图分类号:

S855.3

李笨, 郭富强, 王伟伟, 金宁一, 金秋实, 米志强, 李昌, 王茂鹏. 基于高通量测序和小分子核苷类似物诊断与治疗猫传染性腹膜炎病例转归[J]. 畜牧兽医学报, 2022, 53(1): 200-208.

LI Ben, GUO Fuqiang, WANG Weiwei, JIN Ningyi, JIN Qiushi, MI Zhiqiang, LI Chang, WANG Maopeng. A Case Report of Feline Infectious Peritonitis based on High-throughput Sequencing Diagnosis and Small-molecule Nucleoside Analogues Treatment[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(1): 200-208.

参考文献 30

[1]	PEDERSEN N C, ALLEN C E, LYONS L A. Pathogenesis of feline enteric coronavirus infection[J]. J Feline Med Surg, 2008, 10(6):529-541.
[2]	VOGEL L, VAN DER LUBBEN M, TE LINTELO E G, et al. Pathogenic characteristics of persistent feline enteric coronavirus infection in cats[J]. Vet Res, 2010, 41(5):71.
[3]	BANK-WOLF B R, STALLKAMP I, WIESE S, et al. Mutations of 3c and spike protein genes correlate with the occurrence of feline infectious peritonitis[J]. Vet Microbiol, 2014, 173(3-4):177-188.
[4]	POLAND A M, VENNEMA H, FOLEY J E, et al. Two related strains of feline infectious peritonitis virus isolated from immunocompromised cats infected with a feline enteric coronavirus[J]. J Clin Microbiol, 1996, 34(12):3180-3184.
[5]	TEKES G, THIEL H J. Chapter six - feline coronaviruses:pathogenesis of feline infectious peritonitis[J]. Adv Virus Res, 2016, 96:193-218.
[6]	陶军, 殷方芝, 黄忠, 等. 一例猫传染性腹膜炎病例的诊断和治疗[J]. 上海畜牧兽医通讯, 2021(1):57-58.TAO J, YIN F Z, HUANG Z, et al. Diagnosis and therapy on a cat with feline infectious peritonitis[J]. Journal of Animal Husbandry and Veterinary Communication of Shanghai, 2021(1):57-58. (in Chinese)
[7]	乔石, 陈银亮, 马玉芳. 一例猫传染性腹膜炎的诊治报告[J]. 中兽医医药杂志, 2019, 38(6):84-86.QIAO S, CHEN Y L, MA Y F. A case report of feline infectious peritonitis’ diagnosis and treatment[J]. Journal of Traditional Chinese Veterinary Medicine, 2019, 38(6):84-86. (in Chinese)
[8]	CHANG H W, EGBERINK H F, HALPIN R, et al. Spike protein fusion peptide and feline coronavirus virulence[J]. Emerg Infect Dis, 2012, 18(7):1089-1095.
[9]	WANG J H, HAN Y L, FENG J. Metagenomic next-generation sequencing for mixed pulmonary infection diagnosis[J]. BMC Pulm Med, 2019, 19(1):252.
[10]	SINKOV V V, OGARKOV O B, PLOTNIKOV A O, et al. Metagenomic analysis of mycobacterial transrenal DNA in patients with HIV and tuberculosis coinfection[J]. Infect, Genet Evol, 2020, 77:104057.
[11]	HAN D S, LI Z Y, LI R, et al. mNGS in clinical microbiology laboratories:on the road to maturity[J]. Crit Rev Microbiol, 2019, 45(5-6):668-685.
[12]	SHEAHAN T P, SIMS A C, GRAHAM R L, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses[J]. Sci Transl Med, 2017, 9(396):eaal3653.
[13]	WARREN T K, JORDAN R, LO M K, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys[J]. Nature, 2016, 531(7594):381-385.
[14]	CHEN S F, ZHOU Y Q, CHEN Y R, et al. Fastp:an ultra-fast all-in-one FASTQ preprocessor[J]. Bioinformatics, 2018, 34(17):884-890.
[15]	WOOD D E, LU J, LANGMEAD B. Improved metagenomic analysis with Kraken 2[J]. Genome Biol, 2019, 20(1):257.
[16]	HU Y W, HU S M, WANG W L, et al. Earliest evidence for commensal processes of cat domestication[J]. Proc Nat Acad Sci U S A, 2014, 111(1):116-120.
[17]	STUETZER B, HARTMANN K. Feline parvovirus infection and associated diseases[J]. Vet J, 2014, 201(2):150-155.
[18]	赵艳丽，董宏伟，陈小庆，等.猫杯状病毒反向遗传操作系统的建立及其应用的研究进展[J].病毒学报，2015，31(1)：74-79.ZHAO Y L, DONG H W, CHEN X Q, et al. Progress in establishment and application of feline calicivirus reverse genetics operating system[J]. Chinese Journal of Virology, 2015, 31(1):74-79.(in Chinese)
[19]	STOUT A E, ANDRÉ N M, JAIMES J A, et al. Coronaviruses in cats and other companion animals:Where does SARS-CoV-2/COVID-19 fit?[J]. Vet Microbiol, 2020, 247:108777.
[20]	LEWIS C S, PORTER E, MATTHEWS D, et al. Genotyping coronaviruses associated with feline infectious peritonitis[J]. J Gen Virol, 2015, 96(6):1358-1368.
[21]	SHI J Z, WEN Z Y, ZHONG G X, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2[J]. Science, 2020, 368(6494):1016-1020.
[22]	MCKAY L A, MEACHEM M, SNEAD E, et al. Prevalence and mutation analysis of the spike protein in feline enteric coronavirus and feline infectious peritonitis detected in household and shelter cats in western Canada[J]. Can J Vet Res, 2020, 84(1):18-23.
[23]	YIN Y Y, LI T, WANG C H, et al. A retrospective study of clinical and laboratory features and treatment on cats highly suspected of feline infectious peritonitis in Wuhan, China[J]. Sci Rep, 2021, 11(1):5208.
[24]	SHI Y J, SHUAI L, WEN Z Y, et al. The preclinical inhibitor GS441524 in combination with GC376 efficaciously inhibited the proliferation of SARS-CoV-2 in the mouse respiratory tract[J]. Emerg Microbes Infect, 2021, 10(1):481-492.
[25]	YE G, WANG X W, TONG X H, et al. Structural basis for inhibiting porcine epidemic diarrhea virus replication with the 3C-like protease inhibitor GC376[J]. Viruses, 2020, 12(2):240.
[26]	CHO A, SAUNDERS O L, BUTLER T, et al. Synthesis and antiviral activity of a series of 1’-substituted 4-aza-7, 9-dideazaadenosine C-nucleosides[J]. Bioorg Med Chem Lett, 2012, 22(8):2705-2707.
[27]	MURPHY B G, PERRON M, MURAKAMI E, et al. The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies[J]. Vet Microbiol, 2018, 219:226-233.
[28]	PEDERSEN N C, PERRON M, BANNASCH M, et al. Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis[J]. J Feline Med Surg, 2019, 21(4):271-281.
[29]	PEDERSEN N C, KIM Y, LIU H W, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis[J]. J Feline Med Surg, 2018, 20(4):378-392.
[30]	PERERA K D, RATHNAYAKE A D, LIU H W, et al. Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor[J]. Vet Microbiol, 2019, 237:108398.

基于高通量测序和小分子核苷类似物诊断与治疗猫传染性腹膜炎病例转归

A Case Report of Feline Infectious Peritonitis based on High-throughput Sequencing Diagnosis and Small-molecule Nucleoside Analogues Treatment

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 30

相关文章 2

编辑推荐

Metrics

本文评价

[1]	吴祎程, 冉涛, 周传社, 谭支良. 宏基因组学技术分析山羊瘤胃病毒的多样性[J]. 畜牧兽医学报, 2023, 54(7): 2932-2941.
[2]	尹伊娅, 刘晓雅, 王朝好, 李婷, 胡长敏. 猫传染性腹膜炎研究进展[J]. 畜牧兽医学报, 2020, 51(5): 933-942.