Nutritional status impacts dengue virus infection in mice
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RESEARCH ARTICLE
Open Access
Nutritional status impacts dengue virus infection in mice Christina Chuong1, Tyler A. Bates1, Shamima Akter1,2, Stephen R. Werre3, Tanya LeRoith1 and James Weger-Lucarelli1*
Abstract Background: Dengue virus (DENV) is estimated to infect 390 million people annually. However, few host factors that alter disease severity are known. Malnutrition, defined as both over- and undernutrition, is a growing problem worldwide and has long been linked to dengue disease severity by epidemiological and anecdotal observations. Accordingly, we sought to establish a mouse model to assess the impact of nutritional status on DENV disease severity. Results: Using transiently immunocompromised mice, we established a model of mild dengue disease with measurable viremia. We then applied it to study the effects of healthy weight, obese, and low-protein diets representing normal, over-, and undernutrition, respectively. Upon infection with DENV serotype 2, obese mice experienced more severe morbidity in the form of weight loss and thrombocytopenia compared to healthy weight groups. Additionally, obesity altered cytokine expression following DENV infection. Although low protein-fed mice did not lose significant weight after DENV2 infection, they also experienced a reduction in platelets as well as increased spleen pathology and viral titers. Conclusions: Our results indicate that obese or undernourished mice incur greater disease severity after DENV infection. These studies establish a role for nutritional status in DENV disease severity. Keywords: Dengue virus, Arbovirus, Nutrition, Malnutrition, Nutritional immunology, Disease severity
Background Worldwide, dengue virus (DENV) infects approximately 390 million people each year and is arguably the most significant arthropod-borne viral (arbovirus) threat [1]. Mild dengue disease symptoms include fever accompanied by myalgia, headache, and retro-orbital pain. Severe dengue disease manifestations include hemorrhage and shock, generally accompanied by thrombocytopenia, producing some 500,000 hospitalizations annually, mostly among children. Four DENV serotypes circulate worldwide, and prior infection with another serotype is the most significant risk factor for developing severe dengue disease [2–4]. DENV remains a neglected * Correspondence: [email protected] 1 Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Full list of author information is available at the end of the article
tropical disease despite its growing incidence globally; identifying additional risk factors for severe disease is essential for reducing DENV disease burden. Alongside the increasing incidence of DENV, malnutrition—in the form of under- and overnutrition—is a growing concern globally. According to the World Health Organization (WHO), more than 1.9 billion adults are overweight or obese, while 462 million are underweight [5]. Several studies have found a link between DENV disease severity and nutritional status in
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