Abstract
Dengue virus is a significant public health threat worldwide; however, the pathogenesis of dengue disease remains poorly understood due to lack of appropriate small animal models. Tree shrews are an emerging experimental animal model for the study of human diseases due to their resemblance of genetic characteristics to primate animals. Herein we report that dengue infection in tree shrews elicits resemble clinical symptoms as in humans. Dengue fever (△2°C> normal body temperature) developed in ~22% healthy Chinese tree shrews from 2 through 33 days after infection with a low dose (1 ∗ 104 PFU/animal) of dengue virus serotype 2 or 3 intravenously or subcutaneously. The dengue genomic RNA and neutralizing antibodies were detected in ~78% of animals at days 7 and 15 post infection respectively. The serum levels of liver enzymes including aspartate transaminase, alanine aminotransferase and alkaline phosphatase were elevated with peaks at day 7 after infection. Modest thrombocytopenia and a slight decrease in the white blood cell count were observed. Intriguingly, although viral RNA was barely detectable in the liver by 48 days after infection, it was still evident in the brain. The intra-brain bleeding lesions in the intravenous infection group were more severe than those in the subcutaneous infection group. Our data demonstrate that primary dengue virus infection in tree shrews causes resemble clinical disease as in humans and thus tree shrews may be a suitable model for the study of dengue disease pathogenesis.
Highlights
Dengue infection is one of the major public burdens in the tropical and subtropical areas worldwide, in south Asia, Africa, central and south America
There have been some studies on the dengue virus (DENV) infection model in nonhuman primates (NHP)
Development of a suitable animal model for DENV disease is important for understanding pathogenesis [7]
Summary
Dengue infection is one of the major public burdens in the tropical and subtropical areas worldwide, in south Asia, Africa, central and south America. 3.6 billion people in these areas are at risk for epidemic transmission. 400 million people in more than 100 countries are infected with dengue each year [1]. This significant public health threat is no longer confined to the traditional districts, and autochthonous dengue transmission has been recorded in several European countries [2]. Despite the public health significance of dengue disease, there are still no highly effective vaccines and antiviral drugs. A major obstacle to the development of vaccines and therapeutics is the lack of Abbreviations: DENV, dengue virus; NHP: nonhuman primates; DF, dengue fever
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