Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral I
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RESEARCH ARTICLE
Establishment of Murine Infection Models with Biological Clones of Dengue Viruses Derived from a Single Clinical Viral Isolate Zhihang Zheng1,2,3 • Min Li1 • Zhihua Liu1,2,3 • Xia Jin1,3
•
Jin Sun1
Received: 9 November 2019 / Accepted: 11 March 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Dengue virus (DENV) is a single-stranded RNA virus transmitted by mosquitoes in tropical and subtropical regions. It causes dengue fever, dengue hemorrhagic fever and dengue shock syndrome in patients. Each year, 390 million people are estimated to be infected by four serotypes of dengue virus, creating a great burden on global public health and local economy. So far, no antiviral drug is available for dengue disease, and the newly licensed vaccine is far from satisfactory. One large obstacle for dengue vaccine and drug development is the lack of suitable small animal models. Although some DENV infection models have been developed, only a small number of viral strains can infect immunodeficient mice. In this study, with biologically cloned viruses from a single clinical isolate, we have established two mouse models of DENV infection, one is severe lethal infection in immunocompromised mice, and the other resembles self-limited disease manifestations in Balb/c mice with transient blockage of type I IFN responses. This study not only offers new small animal models of dengue viral infection, but also provides new viral variants for further investigations on dengue viral pathogenesis. Keywords Dengue virus (DENV) Clinical isolate Murine model Interferon deficiency
Introduction Dengue virus (DENV) is an arbovirus transmitted by Aedes aegypti and Aedes albopictus mosquitoes. It belongs to Flavivirus genus of Flaviviridae family and contains a positive single-stranded RNA genome. DENV can be antigenically classified into four serotypes (DENV-1–4), which are often co-circulating in the endemic regions with similar clinical manifestations. Though the majority of DENV infections are asymptomatic, a minority of which & Xia Jin [email protected] & Jin Sun [email protected] 1
CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, 200031 Shanghai, China
2
Chinese Academy of Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China
3
Shanghai Public Health Clinical Center, Fudan University, 201508 Shanghai, China
can result in self-limited disease including dengue fever (DF), and less than 1% may develop into dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Because of the global warming, increased air travel, and the lack of an efficacious vaccine, DENV has become the most prevalent mosquito-borne viral pathogen in recent decades (Guzman et al. 2010). Each year, DENV is estimated to infect 390 million people globally, affecting nearly half of the world population. Asia accounts for 75% of the dengue disease burden, followed by
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