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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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.