广东省柯萨奇病毒A6型重组株与非重组株感染乳鼠生物学特性比较研究

doi:10.12183/j.scjpm.2025.0293

Abstract

Abstract: Objective To analyze the biological characteristics of recombinant and non-recombinant strains of Coxsackievirus A6 (CVA6) in a suckling mice model in Guangdong Province, providing the scientific evidence for the study of the pathogenic mechanism of CVA6. Methods The CVA6 recombinant strain and non-recombinant strain were used to infect the suckling mice model respectively. Then the pathogenicity, tissue viral load, histopathological analysis, immunohistochemical analysis, and cytokine levels of infected suckling mice were compared. Results The median survival time of the CVA6 recombinant strain group (3 days post-infection, dpi) was shorter than that in the CVA6 non-recombinant strain group (6 dpi) (P<0.01). The virus could be detected in multiple tissues of both groups of infected mice, and the viral load in lung tissue of the CVA6 recombinant strain group being 1.78 times that of the CVA6 non-recombinant strain group. Both groups of infected suckling mice showed multi-organ damage, with viral antigens diffusely distributed in skeletal muscle fibers. The IHC staining of the CVA6 recombinant strain group was more obvious than that of the non-recombinant strain group. Muscle damage was present in both groups, with skeletal muscle atrophy in CVA6 recombinant strain group and myolysis in CVA6 non-recombinant strain group. IL-6, IL-10, IFN-γ, and TNF-α were detected in the plasma of both infected mice groups. The decreased level of IL-6 in the CVA6 recombinant strain group lower than that in the CVA6 non-recombinant strain group, and on the 4th day, the level of IL-6 in the CVA6 recombinant strain group (22.17 pg/ml) was significantly higher than that in the CVA6 non-recombinant strain group (3.09 pg/ml) (P<0.01). The content of IFN-γ in the CVA6 non-recombinant strain group was significantly higher than that in the CVA6 recombinant strain group on days 1-2. The levels of IL-10 and TNF-α showed no significant differences (both P>0.05). Conclusions The survival rate of mice infected with the CVA6 recombinant strain in Guangdong Province is significantly lower than that of the non-recombinant strain. There are differences in the effects of both strains on the cytokines IL-6 and IFN-γ.

Key words: Coxsackievirus A6, Suckling mice model, Biological characteristics, Recombination

CLC Number:

R115

XIE Chunyan, ZENG Huiling, LU Jing, LIAN Huimin, QIU Ming, YANG Mingda, YANG Haiyi, QU Lin, DENG Wenwen, LI Shuling, CAO Jiadian, CHEN Zhaolin, YAN Yuxi, YI Lina. Comparison of the biological characteristics of recombinant and non-recombinant Coxsackievirus A6 strains infecting sucking mice in Guangdong Province[J].South China Journal of Preventive Medicine, 2025, 51(3): 293-297.

References

[1] 韦欢欢,朱俊萍. 柯萨奇病毒A组6型分子进化与其相关手足口病流行的研究[J]. 微生物学免疫学进展,2024,52(1):72-78.
[2] Hu L, Maimaiti H, Zhou L, et al.Changing serotypes of hand, foot and mouth disease in Shanghai, 2017-2019[J]. Gut Pathog, 2022, 14(1): 12.
[3] LI JF, Zhang CJ, Li YW, et al.Coxsackievirus A6 was the most common enterovirus serotype causing hand, foot, and mouth disease in Shiyan City, Central China[J]. World J Clin Cases, 2022, 10(31): 11358-11370.
[4] Song Y, Zhang Y, Han Z, et al. Genetic recombination in fast-spreading coxsackievirus A6 variants: A potential role in evolution and pathogenicity[J]. Virus Evol, 2020, 6(2): veaa048.
[5] Andrés C, Guasch E, Piñana M, et al.Recombinant CV-A6 strains related to hand-foot-mouth disease and herpangina at primary care centers (Barcelona, Spain)[J]. Future Microbiol, 2019, 14: 499-507.
[6] Fu X, Wan Z, Li Y, et al.National epidemiology and evolutionary history of four hand, foot and mouth disease-related enteroviruses in China from 2008 to 2016[J]. Virol Sin, 2020, 35(1): 21-33.
[7] He S, Chen M, Wu W, et al.An emerging and expanding clade accounts for the persistent outbreak of coxsackievirus A6-associated hand, foot, and mouth disease in China since 2013[J]. Virology, 2018, 518: 328-334.
[8] 姬桐,李慧,张志晓,等. 低剂量IL-2注射对EV-A71乳鼠感染模型的影响[J]. 病毒学报,2022,38(4):866-873.
[9] Wu Y, Qu Z, Xiong R, et al.A practical method for evaluating the in vivo efficacy of EVA-71 vaccine using a hSCARB2 knock-in mouse model[J]. Emerg Microbes Infect, 2021, 10(1): 1180-1190.
[10] Sun Q, Li J, Wang R, et al.Coxsackievirus A6 infection causes neurogenic pathogenesis in a neonatal murine model[J]. Viruses, 2023, 15(2): 511.
[11] Wang Y, Zou W, Niu Y, et al.Phosphorylation of enteroviral 2A(pro) at Ser/Thr125 benefits its proteolytic activity and viral pathogenesis[J]. J Med Virol, 2023, 95(1): e28400.
[12] Zhang Z, Dong Z, Wei Q, et al.A neonatal murine model of coxsackievirus A6 infection for evaluation of antiviral and vaccine efficacy[J]. J Virol, 2017, 91(9): e02450-16.
[13] Zhu P, Ji W, Li D, et al.Current status of hand-foot-and-mouth disease[J]. J Biomed Sci, 2023, 30(1): 15.
[14] 曾汉日,陆靖,郑焕英,等. 中国广东省18株柯萨奇病毒A6型分离株全基因组特征分析[J]. 病毒学报,2016,32(5):566-573.
[15] Jiang Z, Zhang Y, Lin H, et al.A 10-day-old murine model of coxsackievirus A6 infection for the evaluation of vaccines and antiviral drugs[J]. Front Immunol, 2021, 12: 665197.
[16] Qian SS, Wei ZN, Jin WP, et al.Efficacy of a coxsackievirus A6 vaccine candidate in an actively immunized mouse model[J]. Emerg Microbes Infect, 2021, 10(1): 763-773.
[17] Sun H, Gao M, Cui D, et al.Molecular characteristics of the VP1 region of enterovirus 71 strains in China[J]. Gut Pathog, 2020, 12: 38.
[18] Li D, Sun T, Tao L, et al.A mouse-adapted CVA6 strain exhibits neurotropism and triggers systemic manifestations in a novel murine model[J]. Emerg Microbes Infect, 2022, 11(1): 2248-2263.
[19] Zhang Z, Zhang X, Carr MJ, et al.A neonatal murine model of coxsackievirus A4 infection for evaluation of vaccines and antiviral drugs[J]. Emerg Microbes Infect, 2019, 8(1): 1445-1455.
[20] 赵晓莉,李慧,宋宇,等. 儿童EV71型手足口病血清内皮素-1和炎性因子水平及其与重型发病的关系[J]. 中华医院感染学杂志,2023,33(6):929-932.
[21] Li YS, Ren HC, Cao JH, et al.Roles of interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases[J]. Int Immunopharmacol, 2022, 110: 109005.
[22] 王丽春,廖芸,王晶晶,等. 白细胞介素-6对肠道病毒71型感染乳鼠致病理损伤的促进作用[J]. 中国生物制品学杂志,2014,27(6):761-763,769.
[23] Zhang W, Huang Z, Huang M, et al.Predicting severe enterovirus 71-infected hand, foot, and mouth disease: Cytokines and chemokines[J]. Mediators Inflamm, 2020, 2020: 9273241.
[24] Langer V, Vivi E, Regensburger D, et al.IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin-directed vascular barrier disruption[J]. J Clin Invest, 2019, 129(11): 4691-4707.
[25] Ye N, Gong X, Pang LL, et al.Cytokine responses and correlations thereof with clinical profiles in children with enterovirus 71 infections[J]. BMC Infect Dis, 2015, 15: 225.

Comparison of the biological characteristics of recombinant and non-recombinant Coxsackievirus A6 strains infecting sucking mice in Guangdong Province

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