The Association between Hantavirus Infection and Selenium Deficiency in Mainland China

Li-Qun Fang,Song Liang,Xin-Lou Li,Shu-Qing Zuo,Sake De Vlas,Jia-Qi Ma,Sabra Klein,Kun Liu,Gregory Glass,Li-Ping Wang,Wu-Chun Cao,Marco Goeijenbier,Peng Gong,Lu Liang,Eric Van Gorp,Jan Richardus

doi:10.3390/v7010333

Abstract

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.

Highlights

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease with a severe clinical presentation characterized by, as the name suggests, fever and renal failure potentially complicated by hemorrhage and shock [1]
By analyzing all reported HFRS cases in Mainland China during a six-year period, we found that the annual HFRS
After adjusting for other influential factors, the incidence of HFRS remained statistically significantly associated with selenium deficiency

Summary

Introduction

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease with a severe clinical presentation characterized by, as the name suggests, fever and renal failure potentially complicated by hemorrhage and shock [1]. The disease is the result of infection with an Old-World pathogenic hantavirus, which are negative sensed, single stranded RNA viruses of the genus Hantavirus, a member of the Bunyaviridae family [2]. Pathogenic hantaviruses are shed in the excreta of their reservoir rodents and in most cases each hantavirus is associated with a specific rodent host [3]. In Mainland China, HFRS is either caused by infection with Hantaan virus (HTNV) or Seoul virus (SEOV) carried by striped field mice (Apodemus agrarius) and Norway rats (Rattus rattus), respectively [4,5,6,7]. HFRS is a significant public health problem in Mainland China with an annual average incidence reported up to 120 per.

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