Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea

Park, Sun-Whan; Song, Bong Gu; Shin, E-Hyun; Yun, Sijung; Han, Myung Guk; Park, Mi Yeoun; Park, Chan; Ryou, Jungsang

doi:10.1016/j.ttbdis.2014.07.020

Cited by 120 publications

(113 citation statements)

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“…The virus emerged in rural areas of Hubei province, China, in 2009, and since that time the virus has been detected in many other areas throughout China; subsequently, isolation from patients, coupled with retrospective serological studies, has revealed the presence of the virus in Japan and South Korea as well (18)(19)(20). Here we describe the development of a reverse genetics system that allows the recovery of infectious viruses entirely from transfected cDNA clones.…”

Section: Discussionmentioning

confidence: 99%

“…Detection of SFTSV RNA was highest in H. longicornis, a species that has a widespread geographical distribution outside China including Korea, Japan, Australia, New Zealand, and the Pacific Islands (17). The subsequent reports of SFTSV-positive ticks and confirmed cases of disease in South Korea (18,19) and Japan (20) indicate that SFTSV and SFTSV-like viruses may have a broad geographical distribution.…”

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confidence: 98%

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Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Brennan

Zhang

et al. 2015

J Virol

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Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that was first reported in China in 2009. Phylogenetic analysis of the viral genome showed that SFTS virus represents a new lineage within the Phlebovirus genus, distinct from the existing sandfly fever and Uukuniemi virus groups, in the family Bunyaviridae. SFTS disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 2 to 15%. Here we report the development of reverse genetics systems to study STFSV replication and pathogenesis. We developed and optimized functional T7 polymerase-based M-and S-segment minigenome assays, which revealed errors in the published terminal sequences of the S segment of the Hubei 29 strain of SFTSV. We then generated recombinant viruses from cloned cDNAs prepared to the antigenomic RNAs both of the minimally passaged virus (HB29) and of a cell culture-adapted strain designated HB29pp. The growth properties, pattern of viral protein synthesis, and subcellular localization of viral N and NSs proteins of wild-type HB29pp (wtHB29pp) and recombinant HB29pp viruses were indistinguishable. We also show that the viruses fail to shut off host cell polypeptide production. The robust reverse genetics system described will be a valuable tool for the design of therapeutics and the development of killed and attenuated vaccines against this important emerging pathogen. IMPORTANCESFTSV and related tick-borne phleboviruses such as Heartland virus are emerging viruses shown to cause severe disease in humans in the Far East and the United States, respectively. Study of these novel pathogens would be facilitated by technology to manipulate these viruses in a laboratory setting using reverse genetics. Here, we report the generation of infectious SFTSV from cDNA clones and demonstrate that the behavior of recombinant viruses is similar to that of the wild type. This advance will allow for further dissection of the roles of each of the viral proteins in the context of virus infection, as well as help in the development of antiviral drugs and protective vaccines.T he family Bunyaviridae is one of the largest taxonomic groupings of RNA viruses, containing over 350 named isolates that are classified into five genera: Hantavirus, Nairovirus, Orthobunyavirus, Phlebovirus, and Tospovirus (1). All viruses share a genome structure that comprises three segments of negative-sense or ambisense RNA, named small (S), medium (M), and large (L). The S segment encodes the nucleocapsid (N) protein; the M segment encodes the virion glycoproteins Gn and Gc; and the L segment encodes the L protein, the viral RNA-dependent RNA polymerase. Some viruses also encode nonstructural proteins on the S and M segments. Viruses that impinge on human health, either directly by causing human disease or indirectly by causing economic losses of domestic animals or crop plants, are found in each of the five gener...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Brennan

Zhang

et al. 2015

J Virol

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“…H2A12 was the major binding site of N protein for most human and mouse MAbs. Guo et al [11] confirms that a human monoclonal antibody [6,7], has shown neutralizing activity against SFTSV in vitro and might be used for high risk people in the future. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism.…”

Section: Treatmentmentioning

confidence: 87%

“…Epidemiological study shows that 1.0%-3.8% of the examined population in hilly areas had SFTSV antibodies, which suggests that SFTSV has circulated widely in China, especially in rural areas [5]. SFTSV infection was also reported in other Asia countries such as Korea and Japan [6,7]. The mortality of SFTSV infection in China is about 2.5%-30% [8].…”

mentioning

confidence: 94%

A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

Chen¹

2015

J Antivir Antiretrovir

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IntroductionSFTSV is a newly discovered virus that was first reported in 2009 in China [1]. It was known as Huaiyangshan virus which is a new member of the Phlebovirus genus from the Bunyaviridae family [1]. Clinically, SFTSV can cause fever, gastrointestinal symptoms, myalgia, and regional lymphadenopathy [2]. The most significant manifestations of this disease are severe fever and thrombocytopenia [3]. The disease which could be transmitted through ticks has been found in many cities in China now, and the highest numbers of reported cases were in Henan (48% of the total), Hubei (22%), and Shangdong (16%) [4]. Epidemiological study shows that 1.0%-3.8% of the examined population in hilly areas had SFTSV antibodies, which suggests that SFTSV has circulated widely in China, especially in rural areas [5]. SFTSV infection was also reported in other Asia countries such as Korea and Japan [6,7]. The mortality of SFTSV infection in China is about 2.5%-30% [8]. Most patients are farmers who come from rural areas. Many of them have reported tick bites 7-9 days before getting illness. The disease occurs mainly in April and May during the peaking season in Henan [9]. One study indicated that SFTSV could cause the asymptomatic infections via person-to-person contact with infected blood [6]. At present; there is no specific medication to treat this disease. Patients are often treated with Ribavirin, a traditional nonspecific antiviral drug, but its efficacy remains uncertain [10].There is also report says that antibodies play an important role in curing the disease [11]. Neutralizing antibodies can reduce viral load, and prevent SFTSV spreading. A human monoclonal antibody, 4-5, has been shown to have neutralizing activity against SFTSV in vitro and it might be used for high risk people in the future [11]. For now, there is no effective vaccine to prevent SFTSV infection, so people living in rural areas should pay special attention to this virus, taking some preventive measures, for example protection against tick bites, avoidance of wooded and bushy areas where ticks are abundant, especially in April or May. Repellents, such as permethrin can also be applied [12,13]. SFTSV is susceptible to acid, heat, ether, sodium deoxycholate, other common disinfectants, and ultraviolet irradiation, and can be rapidly inactivated [14][15][16][17][18][19]. . M segment encodes the Gn and Gc which mediate SFTSV entry into human and animal cell lines [16]. Most recently, it has been shown that the lectin dendritic-cellspecific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) facilitates certain Phleboviruses entry into dendritic cells via Gn/Gc mediation, and over-expression of DC-SIGN was sufficient for SFTSV Gn/Gc-mediated entry into otherwise non-susceptible cells [22]. Glycoproteins encoded by M segment are also excellent targets for neutralizing antibodies [17]. Monocytic cells (THP-1), HEF, and cervical carcinoma (Hela) cells were resistant to SFTSV Gn/Gc mediated entry, which indicating that these cells may lack the ...

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“…Although the symptoms of SFTS are mainly nonspecific, drastic loss of white blood cells and platelets are reported in most cases, and multiorgan failure can occur in severe cases, which usually are fatal (10,11). SFTSV has also been isolated from patients in Korea and Japan since 2013 (12)(13)(14)(15). The closely related Heartland virus was characterized after its isolation from two febrile patients in Missouri (16 -18) and has been blamed for at least eight cases of Heartland disease with two fatalities in three more states since 2012.…”

Section: Synaptogyrin-2 (Syngr2)mentioning

confidence: 99%

Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs

Sun

Zhang

et al. 2016

Journal of Biological Chemistry

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Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNAexpressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection. Synaptogyrin-2 (SYNGR2)2 is a tetraspan vesicle membrane protein (1-3) and a member of the synaptogyrin family. Synaptogyrin-1 and -3, abundantly present in synaptic vesicles, are believed to be involved in various aspects in the synaptic vesicle cycle, including vesicle biogenesis, exocytosis and endocytotic recycling, and neurotransmission (2, 4). They are encoded by multigene classes in mammals and evolutionarily conserved throughout the animal kingdom (5). The synaptogyrin-2 gene transcript of 1.6 kb is expressed at high levels in all tissues, except brain, encoding a protein of 224 amino acids in length (5). However, studies on synaptogyrin-2 have been limited, and the function of this protein is largely unknown.Emerging tick-borne bunyaviruses have been recognized to be a serious threat to public health and include severe fever with thrombocytopenia syndrome virus (SFTSV) (6). Since first identified in 2010 in China (7), SFTSV has caused over 3000 reported cases with mortalities ranging from 5 to 15% and has quickly spread to more than 13 provinces (8, 9). Although the symptoms of SFTS are mainly nonspecific, drastic loss of white blood cells and platelets are reported in most cases, and multiorgan failure can occur in severe cases, which usually are fatal (10, 11). SFTSV has also been isolated from patients in Korea and Japan since 2013 (12-15). The clo...

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Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea

Cited by 120 publications

References 13 publications

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

A Newly Discovered Severe Fever with Thrombocytopenia Syndrome Virus and its Mechanisms in Evading Host Innate Immunity

Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs

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