Severe fever with thrombocytopenia syndrome virus
- Hideki Ebihara, PhD
Hideki Ebihara, PhD
- Chief/Principal Investigator
- National Institutes of Health
- Heinz Feldmann, MD
Heinz Feldmann, MD
- Chief/Principal Investigator
- National Institutes of Health
Severe fever with thrombocytopenia syndrome (SFTS), also known as fever, thrombocytopenia, and leukopenia syndrome (FTLS), is an emerging infectious zoonosis in China, Japan, and South Korea . The causative agent is commonly designated SFTS virus (SFTSV), a newly identified bunyavirus, which appears to be carried by ticks (ie, Haemaphysalis longicornis). The disease is remarkably similar to viral hemorrhagic fevers with a characteristic thrombocytopenia. Heartland virus, isolated from patients in the United States, is a closely related but distinct virus that causes a milder clinical syndrome . There is no treatment or vaccine available.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a new member of the genus Phlebovirus in the family Bunyaviridae [3-5]. The closest relative is Bhanja virus, a tick-borne human pathogenic phlebovirus that causes febrile illness and meningitis . Bunyaviruses are largely spherical, enveloped particles with a diameter of 80 to 120 nm. Particles carry three genomic segments designated large (L), medium (M), and small (S).
The L segment encodes the RNA-dependent RNA polymerase (RdRP), the M segment the glycoproteins Gn and Gc, and the S segment the nucleoprotein (N) and a nonstructural protein (NSs) using an ambisense coding strategy . The N protein encapsidates the genomic RNA; this complex is further associated with the L protein and forms the active transcriptase/replicase complex. The Gn and Gc glycoproteins form a heterodimer and shape the spikes on the surface of the virion. The glycoproteins mediate receptor binding and virus entry and are the target for neutralizing humoral immune responses .
The C-type lectin, DC-SIGN, has been identified as one of the factors for SFTSV attachment and entry into cells . The NSs protein serves as a type-I interferon antagonist that suppresses activation of innate immune responses via the IPS-1/IRF-3 and NF-kappaB pathways.
In 2007, a new disease was recognized in the Huaiyangshan mountain range in China with a case fatality rate of 30 percent [3-5,9]. The disease was termed severe fever with thrombocytopenia syndrome (SFTS) or fever, thrombocytopenia, and leukopenia syndrome (FTLS) [3-5]. A new virus, designated SFTS virus (SFTSV), was isolated from patient blood.
- Liu Q, He B, Huang SY, et al. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis. Lancet Infect Dis 2014; 14:763.
- Pastula DM, Turabelidze G, Yates KF, et al. Notes from the field: Heartland virus disease - United States, 2012-2013. MMWR Morb Mortal Wkly Rep 2014; 63:270.
- Yu XJ, Liang MF, Zhang SY, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med 2011; 364:1523.
- Zhang YZ, Zhou DJ, Xiong Y, et al. Hemorrhagic fever caused by a novel tick-borne Bunyavirus in Huaiyangshan, China. Zhonghua Liu Xing Bing Xue Za Zhi 2011; 32:209.
- Xu B, Liu L, Huang X, et al. Metagenomic analysis of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan Province, China: discovery of a new bunyavirus. PLoS Pathog 2011; 7:e1002369.
- Matsuno K, Weisend C, Travassos da Rosa AP, et al. Characterization of the Bhanja serogroup viruses (Bunyaviridae): a novel species of the genus Phlebovirus and its relationship with other emerging tick-borne phleboviruses. J Virol 2013; 87:3719.
- Plyusnin A, Beaty BJ, Elliott RM, et al. Bunyaviridae. In: Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses, King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ (Eds), Elsevier Academic Press, London 2011. p.725.
- Hofmann H, Li X, Zhang X, et al. Severe fever with thrombocytopenia virus glycoproteins are targeted by neutralizing antibodies and can use DC-SIGN as a receptor for pH-dependent entry into human and animal cell lines. J Virol 2013; 87:4384.
- Feldmann H. Truly emerging--a new disease caused by a novel virus. N Engl J Med 2011; 364:1561.
- Li S, Xue C, Fu Y, et al. Sporadic case infected by severe fever with thrombocytopenia syndrome bunyavirus in a non-epidemic region of China. Biosci Trends 2011; 5:273.
- Zhang L, Wang X, Zhang Y, et al. Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) infections in Zhejiang Province, China. Int J Infect Dis 2013; 17:e137.
- Cui F, Cao HX, Wang L, et al. Clinical and epidemiological study on severe fever with thrombocytopenia syndrome in Yiyuan County, Shandong Province, China. Am J Trop Med Hyg 2013; 88:510.
- Bao CJ, Guo XL, Qi X, et al. A family cluster of infections by a newly recognized bunyavirus in eastern China, 2007: further evidence of person-to-person transmission. Clin Infect Dis 2011; 53:1208.
- Zhang L, Liu Y, Ni D, et al. Nosocomial transmission of human granulocytic anaplasmosis in China. JAMA 2008; 300:2263.
- Takahashi T, Maeda K, Suzuki T, et al. The first identification and retrospective study of Severe Fever with Thrombocytopenia Syndrome in Japan. J Infect Dis 2014; 209:816.
- Yoshikawa T, Shimojima M, Fukushi S, et al. Phylogenetic and Geographic Relationships of Severe Fever With Thrombocytopenia Syndrome Virus in China, South Korea, and Japan. J Infect Dis 2015; 212:889.
- Kim K-H, Yi J, Kim G. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis [Internet]. 2013 Nov. http://dx.doi.org/10.3201/eid1911.130792 (Accessed on August 20, 2013).
- Muehlenbachs A, Fata CR, Lambert AJ, et al. Heartland virus-associated death in tennessee. Clin Infect Dis 2014; 59:845.
- McMullan LK, Folk SM, Kelly AJ, et al. A new phlebovirus associated with severe febrile illness in Missouri. N Engl J Med 2012; 367:834.
- Jiang XL, Wang XJ, Li JD, et al. [Isolation, identification and characterization of SFTS bunyavirus from ticks collected on the surface of domestic animals]. Bing Du Xue Bao 2012; 28:252.
- Liu Y, Huang XY, Du YH, et al. [Survey on ticks and detection of new bunyavirus in some vect in the endemic areas of fever, thrombocytopenia and leukopenia syndrome (FTLS) in Henan province]. Zhonghua Yu Fang Yi Xue Za Zhi 2012; 46:500.
- Jiao Y, Zeng X, Guo X, et al. Preparation and evaluation of recombinant severe fever with thrombocytopenia syndrome virus nucleocapsid protein for detection of total antibodies in human and animal sera by double-antigen sandwich enzyme-linked immunosorbent assay. J Clin Microbiol 2012; 50:372.
- Chen H, Hu K, Zou J, Xiao J. A cluster of cases of human-to-human transmission caused by severe fever with thrombocytopenia syndrome bunyavirus. Int J Infect Dis 2013; 17:e206.
- Liu Y, Li Q, Hu W, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome virus. Vector Borne Zoonotic Dis 2012; 12:156.
- Gai Z, Liang M, Zhang Y, et al. Person-to-person transmission of severe fever with thrombocytopenia syndrome bunyavirus through blood contact. Clin Infect Dis 2012; 54:249.
- Kim WY, Choi W, Park SW, et al. Nosocomial transmission of severe fever with thrombocytopenia syndrome in Korea. Clin Infect Dis 2015; 60:1681.
- Zhang YZ, He YW, Dai YA, et al. Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis 2012; 54:527.
- Gai ZT, Zhang Y, Liang MF, et al. Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. J Infect Dis 2012; 206:1095.
- Wen HL, Zhao L, Zhai S, et al. Severe fever with thrombocytopenia syndrome, Shandong Province, China, 2011. Emerg Infect Dis 2014; 20:1.
- Deng B, Zhang S, Geng Y, et al. Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus. PLoS One 2012; 7:e41365.
- Sun Y, Jin C, Zhan F, et al. Host cytokine storm is associated with disease severity of severe fever with thrombocytopenia syndrome. J Infect Dis 2012; 206:1085.
- Chen XP, Cong ML, Li MH, et al. Infection and pathogenesis of Huaiyangshan virus (a novel tick-borne bunyavirus) in laboratory rodents. J Gen Virol 2012; 93:1288.
- Jin C, Liang M, Ning J, et al. Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model. Proc Natl Acad Sci U S A 2012; 109:10053.
- Liu W, Li H, Lu QB, et al. Candidatus Rickettsia tarasevichiae Infection in Eastern Central China: A Case Series. Ann Intern Med 2016; 164:641.
- Cui L, Ge Y, Qi X, et al. Detection of severe fever with thrombocytopenia syndrome virus by reverse transcription-cross-priming amplification coupled with vertical flow visualization. J Clin Microbiol 2012; 50:3881.
- Sun Y, Liang M, Qu J, et al. Early diagnosis of novel SFTS bunyavirus infection by quantitative real-time RT-PCR assay. J Clin Virol 2012; 53:48.
- Yang G, Li B, Liu L, et al. Development and evaluation of a reverse transcription loop-mediated isothermal amplification assay for rapid detection of a new SFTS bunyavirus. Arch Virol 2012; 157:1779.
- Li Z, Cui L, Zhou M, et al. Development and application of a one-step real-time RT-PCR using a minor-groove-binding probe for the detection of a novel bunyavirus in clinical specimens. J Med Virol 2013; 85:370.
- Yoshikawa T, Fukushi S, Tani H, et al. Sensitive and specific PCR systems for detection of both Chinese and Japanese severe fever with thrombocytopenia syndrome virus strains and prediction of patient survival based on viral load. J Clin Microbiol 2014; 52:3325.
- Lu J, Li C, Zhang FS, et al. [Expression of structural and non-structural proteins of severe fever with thrombocytopenia syndrome bunyavirus]. Bing Du Xue Bao 2011; 27:515.
- Yu L, Zhang L, Sun L, et al. Critical epitopes in the nucleocapsid protein of SFTS virus recognized by a panel of SFTS patients derived human monoclonal antibodies. PLoS One 2012; 7:e38291.
- Liu W, Lu QB, Cui N, et al. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome. Clin Infect Dis 2013; 57:1292.