National University of Singapore, Temasek Lifesciences Laboratory, 1 Research Link, 117604 Singapore.
Royal Hobart Hospital, Department of Microbiology and Molecular Medicine, Hobart, 7004 Tasmania, Australia.
Malays J Pathol. 2024 Apr;46(1):51-62.
Small animal models play an important role in investigating and revealing the molecular determinants and mechanisms underlying neuro-virulence of enterovirus A71 (EV-A71). In our previous study, we successfully developed two mouse cell-line replication competent EV-A71 strains (EV71:TLLm and EV71:TLLmv) which were capable of inducing neuro-invasion in BALB/c mice. The more virulent EV71:TLLmv exhibited ability to induce acute encephalomyelitis accompanied by neurogenic pulmonary oedema. EV71:TLLcho virus strain was generated from EV71:TLLm by a series of passages in CHO-K1 cells. EV71:TLLcho demonstrated a broader range of infectivity across various mammalian cell lines and exhibited complete cytopathic effects (CPE) within 48 hours post-inoculation in comparison to EV71:TLLm or EV71:TLLmv. EV71:TLLcho consistently yielded higher levels of viral replication at all time points examined. In comparison to EV71:TLLm, EV71:TLLcho consistently induced more severe disease and increased mortality in one-week old BALB/c mice. However, unlike mice challenged with EV71:TLLmv, none of the mice challenged with EV71:TLLcho progressed to severe acute encephalomyelitis and developed neurogenic pulmonary oedema.
小动物模型在研究和揭示肠道病毒 A71（EV-A71）的神经毒力的分子决定因素和机制方面发挥着重要作用。在我们之前的研究中，我们成功开发了两种能够在 BALB/c 小鼠中诱导神经侵袭的具有复制能力的小鼠细胞系 EV-A71 株（EV71:TLLm 和 EV71:TLLmv）。毒力更强的 EV71:TLLmv 能够诱导急性脑脊髓炎伴神经源性肺水肿。EV71:TLLcho 病毒株是通过在 CHO-K1 细胞中进行一系列传代从 EV71:TLLm 中产生的。与 EV71:TLLm 或 EV71:TLLmv 相比，EV71:TLLcho 在感染后 48 小时内能够更广泛地感染各种哺乳动物细胞系，并表现出完全的细胞病变效应（CPE）。EV71:TLLcho 在所有检测时间点的病毒复制水平均明显高于 EV71:TLLm。与 EV71:TLLm 相比，EV71:TLLcho 能够在 1 周龄的 BALB/c 小鼠中引起更严重的疾病和更高的死亡率。然而，与感染 EV71:TLLmv 的小鼠不同，感染 EV71:TLLcho 的小鼠均未进展为严重急性脑脊髓炎和神经源性肺水肿。
