title: The association between hantavirus infection and selenium deficiency in mainland China.
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.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. fang_lq@163.com.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Fang
authors.affiliation: Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015CE, The Netherlands. m.goeijenbier@erasmusmc.nl.
authors.forename: Marco
authors.initials: M
authors.lastname: Goeijenbier
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. zuoshq@126.com.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Zuo
authors.affiliation: Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing 102206, China. wanglp@chinacdc.cn.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Environmental and Global Health, College of Public Health and Health Professions, and Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA. ehs.liang@gmail.com.
authors.forename: Song
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. saklein@jhsph.edu.
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. xinlou2010@163.com.
authors.forename: Xin-Lou
authors.initials: XL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. liukun5959@163.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory for Earth System Modeling, and Center for Earth System Science, Tsinghua University, Beijing 100084, China. liang_lu@tsinghua.edu.cn.
authors.forename: Lu
authors.initials: L
authors.lastname: Liang
authors.affiliation: Ministry of Education Key Laboratory for Earth System Modeling, and Center for Earth System Science, Tsinghua University, Beijing 100084, China. penggong@mail.tsinghua.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. ggurrigl@jhsph.edu.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Glass
authors.affiliation: Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015CE, The Netherlands. ecmvangorp@gmail.com.
authors.forename: Eric
authors.initials: E
authors.lastname: van Gorp
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000CA, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Richardus
authors.affiliation: Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3000CA, The Netherlands. majq@chinacdc.cn.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. caowc@bmi.ac.cn.
authors.forename: Wu-Chun
authors.initials: WC
authors.lastname: Cao
authors.affiliation: National Center for Public Health Surveillance and Information Service, Chinese Center for Disease Control and Prevention, Beijing 102206, China. s.devlas@erasmusmc.nl.
authors.forename: Sake J
authors.initials: SJ
authors.lastname: de Vlas
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002681:China; D042783:Endothelial Cells / Q000821:virology; D005260:Female; D006476:Orthohantavirus / Q000254:growth & development; D018778:Hantavirus Infections / Q000453:epidemiology* / Q000662:veterinary*; D006801:Humans; D015994:Incidence; D008297:Male; D012377:Rodentia; D012643:Selenium / Q000172:deficiency*
chemical_list: D012643:Selenium