Transgenic mice expressing the human CDHR3 receptor: A sensitive RV-C infection model for the evaluation of vaccines and therapeutics

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-02-07 DOI:10.1016/j.antiviral.2025.106102

Zhenhong Zhou , Rui Zhu , Hongwei Yang , Weixi Deng , Zijie Zhang , Yue Li , Jiaxin Xu , Ziyang Yan , Ruoxi Wang , Sijia Chang , Zhichao Yin , Yuanyuan Wu , Dongqing Zhang , Mujin Fang , Che Liu , Yuqiong Que , Jun Zhang , Ningshao Xia , Yingbin Wang , Longfa Xu , Tong Cheng

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引用次数: 0

Abstract

Rhinovirus C (RV-C) is the primary causative agent of severe acute respiratory illnesses (ARTIs) in infants and young children. The limited availability of animal models complicates the development of prophylactic and therapeutic strategies targeting RV-C. Previous studies have identified human cadherin-related family member 3 (hCDHR3) as the cellular receptor for RV-C, with its expression enabling previously unsusceptible cells to support both viral entry and replication. Recently, an adult hCDHR3 transgenic mouse model was developed to investigate the role of human stimulator of interferon genes (hSTING) in RV-C15 infection in vivo. However, adult mice do not support efficient RV-C15 infection. Here, we report a transgenic mouse line expressing hCDHR3 constitutively that is highly susceptible to early-life infections by multiple serotypes of RV-C, including RV-C15, RV-C2, and RV-C41. Neonatal transgenic mice infected with various RV-C strains via the intraperitoneal (i.p.) route exhibit similar symptoms, such as severe inflammation, limb paralysis, and death. Moreover, passive immunization with antisera or therapeutic antibodies can protect against lethal RV-C infection in these transgenic mice. Overall, this study provides a valuable animal model for the in vivo antiviral evaluation against RV-C.

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表达人CDHR3受体的转基因小鼠：一种用于评估疫苗和治疗方法的敏感RV-C感染模型

鼻病毒C （RV-C）是婴幼儿严重急性呼吸道疾病（ARTIs）的主要病原体。动物模型的有限可用性使针对RV-C的预防和治疗策略的发展复杂化。先前的研究已经确定人类钙粘蛋白相关家族成员3 （hCDHR3）是RV-C的细胞受体，其表达使以前不敏感的细胞能够支持病毒进入和复制。最近，为了研究人干扰素刺激因子（hSTING）在体内感染RV-C15中的作用，建立了hCDHR3转基因成年小鼠模型。然而，成年小鼠不支持有效的RV-C15感染。在这里，我们报道了一种表达hCDHR3的转基因小鼠系，它对多种血清型RV-C（包括RV-C15、RV-C2和RV-C41）的早期感染高度敏感。通过腹腔（i.p.）途径感染各种RV-C毒株的新生转基因小鼠表现出类似的症状，如严重炎症、肢体瘫痪和死亡。此外，抗血清或治疗性抗体的被动免疫可以保护这些转基因小鼠免受致命的RV-C感染。总之，本研究为体内抗病毒评价提供了一个有价值的动物模型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.