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对Toll样受体对登革病毒感染反应分子机制的最新见解

Recent Insights Into the Molecular Mechanism of Toll-Like Receptor Response to Dengue Virus Infection.

作者信息

Kayesh Mohammad Enamul Hoque, Kohara Michinori, Tsukiyama-Kohara Kyoko

机构信息

Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.

Department of Microbiology and Public Health, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Barishal, Bangladesh.

出版信息

Front Microbiol. 2021 Sep 16;12:744233. doi: 10.3389/fmicb.2021.744233. eCollection 2021.

Abstract

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease caused by dengue virus (DENV). Recently, DENV has been affecting humans within an expanding geographic range due to the warming of the earth. Innate immune responses play a significant role in antiviral defense, and Toll-like receptors (TLRs) are key regulators of innate immunity. Therefore, a detailed understanding of TLR and DENV interactions is important for devising therapeutic and preventive strategies. Several studies have indicated the ability of DENV to modulate the TLR signaling pathway and host immune response. Vaccination is considered one of the most successful medical interventions for preventing viral infections. However, only a partially protective dengue vaccine, the first licensed dengue vaccine CYD-TDV, is available in some dengue-endemic countries to protect against DENV infection. Therefore, the development of a fully protective, durable, and safe DENV vaccine is a priority for global health. Here, we demonstrate the progress made in our understanding of the host response to DENV infection, with a particular focus on TLR response and how DENV avoids the response toward establishing infection. We also discuss dengue vaccine candidates in late-stage development and the issues that must be overcome to enable their success.

摘要

登革热是由登革病毒(DENV)引起的最普遍且传播迅速的蚊媒病毒性疾病。近来,由于地球变暖,登革病毒在不断扩大的地理范围内影响着人类。固有免疫反应在抗病毒防御中发挥着重要作用,而Toll样受体(TLR)是固有免疫的关键调节因子。因此,详细了解TLR与DENV的相互作用对于制定治疗和预防策略至关重要。多项研究表明DENV有能力调节TLR信号通路和宿主免疫反应。疫苗接种被认为是预防病毒感染最成功的医学干预措施之一。然而,在一些登革热流行国家,仅有部分保护性的登革热疫苗(首款获批的登革热疫苗CYD-TDV)可用于预防DENV感染。因此,研发一种具有完全保护作用、持久且安全的DENV疫苗是全球卫生领域的优先事项。在此,我们展示了在理解宿主对DENV感染的反应方面所取得的进展,特别关注TLR反应以及DENV如何规避该反应以建立感染。我们还讨论了处于后期研发阶段的登革热候选疫苗以及使其成功必须克服的问题。

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