The Emergence of Severe Fever with Thrombocytopenia Syndrome Virus

Jesus A. Silvas Department of Pathology, University of Texas Medical Branch, Galveston, Texas;
Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, Texas;

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Patricia V. Aguilar Department of Pathology, University of Texas Medical Branch, Galveston, Texas;
Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, Texas;
Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas

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Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces. In addition, SFTS has been recognized in South Korea and Japan with the first confirmed cases reported in 2012. A similar disease, caused by the closely related Heartland virus, was also reported in the United States in 2009. SFTS is caused by SFTS virus, a novel tick-borne virus in the family Bunyaviridae, genus Phlebovirus. Unlike other mosquito- and sandfly-borne bunyaviruses, SFTS virus has not been extensively studied due to its recent emergence and many unknowns regarding its pathogenesis, life cycle, transmission, and options for therapeutics remains. In this review, we report the most current findings in SFTS virus research.

Author Notes

Address for correspondence to Patricia V. Aguilar, Department of Pathology, Center for Tropical Diseases, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77550. E-mail: pvaguila@utmb.edu

Authors’ addresses: Jesus A. Silvas and Patricia V. Aguilar, Department of Pathology, University of Texas Medical Branch at Galveston, Pathology, Galveston, TX, E-mails: jasilvas@utmb.edu and pvaguila@utmb.edu.

Financial support: This study was supported by the National Institutes of Health (NIH) grants number F31 AI124662-01 and AI115286-01A1. Patricia V. Aguilar was also partially supported by 5R24AI120942-02.

  • 1.

    Yu XJ et al.., 2011. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med 364: 15231532.

  • 2.

    Zhang YZ et al.., 2011. Hemorrhagic fever caused by a novel tick-borne Bunyavirus in Huaiyangshan, China. Zhonghua Liu Xing Bing Xue Za Zhi 32: 209220.

    • Search Google Scholar
    • Export Citation
  • 3.

    Palacios G, Savji N, Travassos da Rosa A, Guzman H, Yu X, Desai A, Rosen GE, Hutchison S, Lipkin WI, Tesh R, 2013. Characterization of the Uukuniemi virus group (Phlebovirus: Bunyaviridae): evidence for seven distinct species. J Virol 87: 31873195.

    • Search Google Scholar
    • Export Citation
  • 4.

    Luo LM et al.., 2015. Haemaphysalis longicornis ticks as reservoir and vector of severe fever with thrombocytopenia syndrome virus in China. Emerg Infect Dis 21: 17701776.

    • Search Google Scholar
    • Export Citation
  • 5.

    Liu K et al.., 2015. A national assessment of the epidemiology of severe fever with thrombocytopenia syndrome, China. Sci Rep 5: 9679.

  • 6.

    Kim KH, Yi J, Kim G, Choi SJ, Jun KI, Kim NH, Choe PG, Kim NJ, Lee JK, Oh MD, 2013. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis 19: 18921894.

    • Search Google Scholar
    • Export Citation
  • 7.

    Takahashi T et al.., 2013. The first identification and retrospective study of severe fever with thrombocytopenia syndrome in Japan. J Infect Dis 209: 816827.

    • Search Google Scholar
    • Export Citation
  • 8.

    Savage HM, Godsey MS, Lambert A, Panella NA, Burkhalter KL, Harmon JR, Lash RR, Ashley DC, Nicholson WL, 2013. First detection of heartland virus (Bunyaviridae: Phlebovirus) from field collected arthropods. Am J Trop Med Hyg 89: 445452.

    • Search Google Scholar
    • Export Citation
  • 9.

    Muehlenbachs A, Fata CR, Lambert AJ, Paddock CD, Velez JO, Blau DM, Staples JE, Karlekar MB, Bhatnagar J, Nasci RS, Zaki SR, 2014. Heartland virus-associated death in Tennessee. Clin Infect Dis 59: 845850.

    • Search Google Scholar
    • Export Citation
  • 10.

    Liu Y, Li Q, Hu W, Wu J, Wang Y, Mei L, Walker DH, Ren J, Yu XJ, 2012. Person-to-person transmission of severe fever with thrombocytopenia syndrome virus. Vector Borne Zoonotic Dis 12: 156160.

    • Search Google Scholar
    • Export Citation
  • 11.

    Ding F et al.., 2013. Epidemiologic features of severe fever with thrombocytopenia syndrome in China, 2011–2012. Clin Infect Dis 56: 16821683.

    • Search Google Scholar
    • Export Citation
  • 12.

    Liu Q, He B, Huang SY, Wei F, Zhu XQ, 2014. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect Dis 14: 763772.

    • Search Google Scholar
    • Export Citation
  • 13.

    Park SW, Han MG, Yun SM, Park C, Lee WJ, Ryou J, 2014. Severe fever with thrombocytopenia syndrome virus, South Korea, 2013. Emerg Infect Dis 20: 18801882.

    • Search Google Scholar
    • Export Citation
  • 14.

    Hiraki T et al.., 2014. Two autopsy cases of severe fever with thrombocytopenia syndrome (SFTS) in Japan: a pathognomonic histological feature and unique complication of SFTS. Pathol Int 64: 569575.

    • Search Google Scholar
    • Export Citation
  • 15.

    Liu K et al.., 2014. Epidemiologic features and environmental risk factors of severe fever with thrombocytopenia syndrome, Xinyang, China. PLoS Negl Trop Dis 8: e2820.

    • Search Google Scholar
    • Export Citation
  • 16.

    Kato H, Yamagishi T, Shimada T, Matsui T, Shimojima M, Saijo M, Oishi K; SFTS Epidemiological Research Group-Japan, 2016. Epidemiological and clinical features of severe fever with thrombocytopenia syndrome in Japan, 2013–2014. PLoS One 11: e0165207.

    • Search Google Scholar
    • Export Citation
  • 17.

    Zhao L et al.., 2012. Severe fever with thrombocytopenia syndrome virus, Shandong Province, China. Emerg Infect Dis 18: 963965.

  • 18.

    Cui F, Cao HX, Wang L, Zhang SF, Ding SJ, Yu XJ, Yu H, 2013. Clinical and epidemiological study on severe fever with thrombocytopenia syndrome in Yiyuan County, Shandong Province, China. Am J Trop Med Hyg 88: 510512.

    • Search Google Scholar
    • Export Citation
  • 19.

    Huang YT, Zhao L, Wen HL, Yang Y, Yu H, Yu XJ, 2016. Neutralizing antibodies to severe fever with thrombocytopenia syndrome virus 4 years after hospitalization, China. Emerg Infect Dis 22: 19851987.

    • Search Google Scholar
    • Export Citation
  • 20.

    Zeng P et al..; International Component of the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III), 2015. A study of seroprevalence and rates of asymptomatic viremia of severe fever with thrombocytopenia syndrome virus among Chinese blood donors. Transfusion 55: 965971.

    • Search Google Scholar
    • Export Citation
  • 21.

    Yun SM, Lee WG, Ryou J, Yang SC, Park SW, Roh JY, Lee YJ, Park C, Han MG, 2014. Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013. Emerg Infect Dis 20: 13581361.

    • Search Google Scholar
    • Export Citation
  • 22.

    Choi SJ et al..; for Korea SFTS Clinical Network, 2016. Severe fever with thrombocytopenia syndrome in South Korea, 2013–2015. PLoS Negl Trop Dis 10: e0005264.

    • Search Google Scholar
    • Export Citation
  • 23.

    Jiao Y, Qi X, Liu D, Zeng X, Han Y, Guo X, Shi Z, Wang H, Zhou M, 2015. Experimental and natural infections of goats with severe fever with thrombocytopenia syndrome virus: evidence for ticks as viral vector. PLoS Negl Trop Dis 9: e0004092.

    • Search Google Scholar
    • Export Citation
  • 24.

    Wang S et al.., 2015. SFTS virus in ticks in an endemic area of China. Am J Trop Med Hyg 92: 684689.

  • 25.

    Zhang YZ et al.., 2011. The ecology, genetic diversity and phylogeny of Huaiyangshan virus in China. J Virol 86: 28642868.

  • 26.

    Li Z et al.., 2016. Ecology of the tick-borne Phlebovirus causing severe fever with thrombocytopenia syndrome in an endemic area of China. PLoS Negl Trop Dis 10: e0004574.

    • Search Google Scholar
    • Export Citation
  • 27.

    Niu G et al.., 2013. Severe fever with thrombocytopenia syndrome virus among domesticated animals, China. Emerg Infect Dis 19: 756763.

  • 28.

    Li Z et al.., 2014. Seroprevalence of antibodies against SFTS virus infection in farmers and animals, Jiangsu, China. J Clin Virol 60: 185189.

    • Search Google Scholar
    • Export Citation
  • 29.

    Hwang J, Kang JG, Oh SS, Chae JB, Cho YK, Cho YS, Lee H, Chae JS, 2016. Molecular detection of severe fever with thrombocytopenia syndrome virus (SFTSV) in feral cats from Seoul, Korea. Ticks Tick Borne Dis 8: 912.

    • Search Google Scholar
    • Export Citation
  • 30.

    Hayasaka D, Fuxun Y, Yoshikawa A, Posadas-Herrera G, Shimada S, Tun MM, Agoh M, Morita K, 2016. Seroepidemiological evidence of severe fever with thrombocytopenia syndrome virus infections in wild boars in Nagasaki, Japan. Trop Med Health 44: 6.

    • Search Google Scholar
    • Export Citation
  • 31.

    Tabara K, Fujita H, Hirata A, Hayasaka D, 2016. Investigation of severe fever with thrombocytopenia syndrome virus antibody among domestic bovines transported to slaughterhouse in Shimane Prefecture, Japan. Jpn J Infect Dis 69: 445447.

    • Search Google Scholar
    • Export Citation
  • 32.

    Yun Y et al.., 2015. Phylogenetic analysis of severe fever with thrombocytopenia syndrome virus in South Korea and migratory bird routes between China, South Korea, and Japan. Am J Trop Med Hyg 93: 468474.

    • Search Google Scholar
    • Export Citation
  • 33.

    Park SW, Song BG, Shin EH, Yun SM, Han MG, Park MY, Park C, Ryou J, 2014. Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea. Ticks Tick Borne Dis 5: 975977.

    • Search Google Scholar
    • Export Citation
  • 34.

    Zhang YZ, Xu J, 2016. The emergence and cross species transmission of newly discovered tick-borne Bunyavirus in China. Curr Opin Virol 16: 126131.

    • Search Google Scholar
    • Export Citation
  • 35.

    Bao CJ et al.., 2011. A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission. Clin Infect Dis 53: 12081214.

    • Search Google Scholar
    • Export Citation
  • 36.

    Jiang XL et al.., 2015. A cluster of person-to-person transmission cases caused by SFTS virus in Penglai, China. Clin Microbiol Infect 21: 274279.

    • Search Google Scholar
    • Export Citation
  • 37.

    Yoo JR, Heo ST, Park D, Kim H, Fukuma A, Fukushi S, Shimojima M, Lee KH, 2016. Family cluster analysis of severe fever with thrombocytopenia syndrome virus infection in Korea. Am J Trop Med Hyg 95: 13511357.

    • Search Google Scholar
    • Export Citation
  • 38.

    Xing X et al.., 2016. Natural transmission model for severe fever with thrombocytopenia syndrome Bunyavirus in villages of Hubei Province, China. Medicine (Baltimore) 95: e2533.

    • Search Google Scholar
    • Export Citation
  • 39.

    Blakqori G et al.., 2007. La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J Virol 81: 49914999.

    • Search Google Scholar
    • Export Citation
  • 40.

    Ikegami T, Narayanan K, Won S, Kamitani W, Peters CJ, Makino S, 2009. Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA transcription and post-transcriptional downregulation of protein kinase PKR. Ann N Y Acad Sci 1171 (Suppl 1): E75E85.

    • Search Google Scholar
    • Export Citation
  • 41.

    Kalveram B, Lihoradova O, Indran SV, Lokugamage N, Head JA, Ikegami T, 2013. Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR. Virology 435: 415424.

    • Search Google Scholar
    • Export Citation
  • 42.

    Leonard VH, Kohl A, Hart TJ, Elliott RM, 2006. Interaction of Bunyamwera Orthobunyavirus NSs protein with mediator protein MED8: a mechanism for inhibiting the interferon response. J Virol 80: 96679675.

    • Search Google Scholar
    • Export Citation
  • 43.

    van Knippenberg I, Carlton-Smith C, Elliott RM, 2010. The N-terminus of Bunyamwera orthobunyavirus NSs protein is essential for interferon antagonism. J Gen Virol 91: 20022006.

    • Search Google Scholar
    • Export Citation
  • 44.

    Weber F, Bridgen A, Fazakerley JK, Streitenfeld H, Kessler N, Randall RE, Elliott RM, 2002. Bunyamwera bunyavirus nonstructural protein NSs counteracts the induction of alpha/beta interferon. J Virol 76: 79497955.

    • Search Google Scholar
    • Export Citation
  • 45.

    Le May N, Mansuroglu Z, Léger P, Josse T, Blot G, Billecocq A, Flick R, Jacob Y, Bonnefoy E, Bouloy M, 2008. A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells. PLoS Pathog 4: e13.

    • Search Google Scholar
    • Export Citation
  • 46.

    Santiago FW, 2014. Hijacking of RIG-I signaling proteins into virus-induced cytoplasmic structures correlates with the inhibition of type I interferon responses. J Virol 88: 45724585.

    • Search Google Scholar
    • Export Citation
  • 47.

    Qu B et al.., 2012. Suppression of the interferon and NF-κB responses by severe fever with thrombocytopenia syndrome virus. J Virol 86: 83888401.

    • Search Google Scholar
    • Export Citation
  • 48.

    Ning YJ, Wang M, Deng M, Shen S, Liu W, Cao WC, Deng F, Wang YY, Hu Z, Wang H, 2014. Viral suppression of innate immunity via spatial isolation of TBK1/IKKE from mitochondrial antiviral platform. J Mol Cell Biol 6: 324337.

    • Search Google Scholar
    • Export Citation
  • 49.

    Ning YJ, Feng K, Min YQ, Cao WC, Wang M, Deng F, Hu Z, Wang H, 2015. Disruption of type I interferon signaling by the nonstructural protein of severe fever with thrombocytopenia syndrome virus via the hijacking of STAT2 and STAT1 into inclusion bodies. J Virol 89: 42274236.

    • Search Google Scholar
    • Export Citation
  • 50.

    Ning YJ, Wang M, Deng M, Shen S, Liu W, Cao WC, Deng F, Wang YY, Hu Z, Wang H, 2014. Viral suppression of innate immunity via spatial isolation of TBK1/IKKΕ from mitochondrial antiviral platform. J Mol Cell Biol 6: 324337.

    • Search Google Scholar
    • Export Citation
  • 51.

    Wu X, Qi X, Liang M, Li C, Cardona CJ, Li D, Xing Z, 2014. Roles of viroplasm-like structures formed by nonstructural protein NSs in infection with severe fever with thrombocytopenia syndrome virus. FASEB J 28: 25042516.

    • Search Google Scholar
    • Export Citation
  • 52.

    Silvas JA, Popov VL, Paulucci-Holthauzen A, Aguilar PV, 2016. Extracellular vesicles mediate receptor-independent transmission of novel tick-borne bunyavirus. J Virol 90: 873886.

    • Search Google Scholar
    • Export Citation
  • 53.

    Sun Y et al.., 2012. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis 206: 10851094.

    • Search Google Scholar
    • Export Citation
  • 54.

    Jin C et al.., 2012. Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model. Proc Natl Acad Sci USA 109: 1005310058.

    • Search Google Scholar
    • Export Citation
  • 55.

    Sun L, Hu Y, Niyonsaba A, Tong Q, Lu L, Li H, Jie S, 2014. Detection and evaluation of immunofunction of patients with severe fever with thrombocytopenia syndrome. Clin Exp Med 14: 389395.

    • Search Google Scholar
    • Export Citation
  • 56.

    Kaneyuki S, Yoshikawa T, Tani H, Fukushi S, Taniguchi S, Fukuma A, Shimojima M, Kurosu T, Morikawa S, Saijo M, 2016. Ulcerative lesions with hemorrhage in a patient with severe fever with thrombocytopenia syndrome observed via upper gastrointestinal endoscopy. Jpn J Infect Dis 69: 525527.

    • Search Google Scholar
    • Export Citation
  • 57.

    Liu MM, Lei XY, Yu XJ, 2016. Meta-analysis of the clinical and laboratory parameters of SFTS patients in China. Virol J 13: 198.

  • 58.

    Liu W et al.., 2013. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in China who had severe fever with thrombocytopenia syndrome. Clin Infect Dis 57: 12921299.

    • Search Google Scholar
    • Export Citation
  • 59.

    Park SY, Choi W, Chong YP, Park SW, Wang EB, Lee WJ, Jee Y, Kwon SW, Kim SH, 2016. Use of plasma therapy for severe fever with thrombocytopenia syndrome encephalopathy. Emerg Infect Dis 22: 13061308.

    • Search Google Scholar
    • Export Citation
  • 60.

    Oh WS, Heo ST, Kim SH, Choi WJ, Han MG, Kim JY, 2014. Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome. Int J Infect Dis 18: 8486.

    • Search Google Scholar
    • Export Citation
  • 61.

    Kim UJ, Kim DM, Ahn JH, Kang SJ, Jang HC, Park KH, Jung SI, 2016. Successful treatment of rapidly progressing severe fever with thrombocytopenia syndrome with neurological complications using intravenous immunoglobulin and corticosteroid. Antivir Ther 21: 637640.

    • Search Google Scholar
    • Export Citation
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