Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy

Saijo, Masayuki

doi:10.1016/j.jiac.2018.07.009

Cited by 74 publications

(66 citation statements)

References 46 publications

(55 reference statements)

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“…SFTSV is genetically closely related to Heartland virus (HRTV), which has been found to cause a severe, and occasionally fatal, febrile illness in humans in cases in the US (2). Increasing incidence of SFTS has led to serious public health concerns in countries throughout East Asia, including China, Japan, and South Korea (3)(4)(5)(6)(7)(8)(9). The typical clinical course of SFTS has 3 distinct periods that are characterized according to disease progression: a fever stage, a multiple-organ-dysfunction (MOD) stage, and a convalescence stage (4,(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Suzuki

Sato

Sano

et al. 2020

Journal of Clinical Investigation

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jp (HS). in vitro experiments using PBMCs and cell lines. MK conducted EM analysis and acquired EM images. SM, SF, TY, M. Shimojima, and M. Saijo provided reagents for histopathological and virological assays. TS wrote the original draft of the manuscript. All authors contributed to reviewing and editing the manuscript. SM and M. Saijo supervised the study and supported analyses. TS and HH supervised the study.

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Section: Introductionmentioning

confidence: 99%

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Suzuki

Sato

Sano

et al. 2020

Journal of Clinical Investigation

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“…The development of specific treatment for SFTS is crucial because SFTSV infection is relatively rare and the affected patients are mainly elderly. Some proposed treatments for SFTS include steroid pulse therapy (Nakamura et al, 2018), plasma exchange (Oh et al, 2014;Yoo et al, 2019), and antiviral drugs (Saijo, 2018); however, their effectiveness remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito

Saijo

2020

Front. Microbiol.

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6-30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents in vitro and in vivo, with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10 6 copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in in vitro assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2 ′ -fluoro-2 ′ -deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy in vitro and in vivo, retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.Keywords: severe fever with thrombocytopenia syndrome, severe fever with thrombocytopenia syndrome virus, antiviral, ribavirin, favipiravir Frontiers in Microbiology | www.frontiersin.org

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“…Autopsies from patients with SFTS and HRTV disease have shown viral antigen present in infiltrating lymphocytes in various tissues, including but not limited to spleen, kidneys, lungs and heart [39][40][41][42]. In particular, specific studies have shown HRTV antigen positive macrophages and Kupffer cells in the liver of a patient with HRTV-associated death [43].…”

Section: Target Tissues/cells and Cellular Receptorsmentioning

confidence: 99%

Immune Modulation and Immune-Mediated Pathogenesis of Emerging Tickborne Banyangviruses

2019

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In the last decade, the emergence of several, novel tickborne viruses have caused significant disease in humans. Of interest are the tickborne banyangviruses: Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV), and Guertu virus (GTV). SFTSV and HRTV infection in humans cause viral hemorrhagic fever-like disease leading to mortality rates ranging from 6–30% of the cases. The systemic inflammatory response syndrome (SIRS) associated with SFTSV infection is hypothesized to contribute significantly to pathology seen in patients. Despite the severe disease caused by HRTV and SFTSV, there are no approved therapeutics or vaccines. Investigation of the immune response during and following infection is critical to the generation of fully protective vaccines and/or supportive treatments, and overall understanding of viral immune evasion mechanisms may aid in the development of a new class of therapeutics.

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Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy

Cited by 74 publications

References 46 publications

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Immune Modulation and Immune-Mediated Pathogenesis of Emerging Tickborne Banyangviruses

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