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

Suzuki, Tadaki; Sato, Yuko; Sano, Kaori; Arashiro, Takeshi; Katano, Harutaka; Nakajima, N.; Shimojima, Masayuki; Kataoka, Michiyo; Takahashi, Keiichi; Wada, Yuji; Morikawa, Shigeru; Fukushi, Shuetsu; Yoshikawa, Tomoki; Saijo, Masayuki; Hasegawa, Hideki

doi:10.1172/jci129171

Cited by 65 publications

(74 citation statements)

References 57 publications

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“…The SFTSV copy number was determined by quantitative real-time RT-PCR on RNA samples extracted from paraffin-embedded sections (10 µm; 3×) as described previously with some modifications [ 3 , 22 ]. Briefly, RNA was extracted using a Pure Link FFPE RNA isolation kit (Invitrogen, Carlsbad, CA, USA), and RT-PCR was performed using a QuantiTect Multiplex RT-PCR Kit (Qiagen, Hilden, Germany) and Agilent Mx3000P system (Agilent, Santa Clara, CA, USA) according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

“…Histopathological studies of formalin-fixed and paraffin-embedded specimens were performed using hematoxylin–eosin staining. Immunohistochemical detection of the SFTSV nucleoprotein antigen (SFTSV-NP) was performed on paraffin-embedded sections, as previously described [ 3 , 22 ]. After deparaffinizing with xylene, sections were rehydrated in ethanol and immersed in PBS.…”

Section: Methodsmentioning

confidence: 99%

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Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite

Tsuru

Suzuki

Murakami

et al. 2021

Viruses

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A woman in her fifties showed symptoms of fever, loss of appetite, vomiting, and general fatigue 2 days after she was bitten by a sick cat, which had later died, in Yamaguchi prefecture, western Japan, in June 2016. She subsequently died of multiorgan failure, and an autopsy was performed to determine the cause of death. However, the etiological pathogens were not quickly identified. The pathological features of the patient were retrospectively re-examined, and the pathology of the regional lymph node at the site of the cat bite was found to show necrotizing lymphadenitis with hemophagocytosis. The pathological features were noted to be similar to those of patients reported to have severe fever with thrombocytopenia syndrome (SFTS). Therefore, the lymph node section was retrospectively tested immunohistochemically, revealing the presence of the SFTS virus (SFTSV) antigen. The sick cat showed similar symptoms and laboratory findings similar to those shown in human SFTS cases. The patient had no history of tick bites, and did not have skin lesions suggestive of these. She had not undertaken any outdoor activities. It is highly possible that the patient was infected with SFTSV through the sick cat’s bite. If a patient gets sick in an SFTS-endemic region after being bitten by a cat, SFTS should be considered in the differential diagnosis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite

Tsuru

Suzuki

Murakami

et al. 2021

Viruses

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“…SFTS virions target the lymphatic system, primarily spleen to target killing of monocytes and thrombocytes (platelets) [21]. SARS-CoV2 targets ACE receptors to make entry in endothelial cell [22] while SFTS virions target lymphoid tissues particularly thrombocytes [23].…”

Section: Introductionmentioning

confidence: 99%

Molecular docking and simulation investigation: effect of beta-sesquiphellandrene with ionic integration on SARS-CoV2 and SFTS viruses

Joshi

Kaushik

2020

Journal of Genetic Engineering and Biotechnology

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Background At present, viral diseases become major concern for the world. SARS-CoV2 and SFTS viruses are deadly in nature, and there is a need for developing best treatments for them. Modern in silico approaches were found to be very handy in determining putative drug molecules. In this study, we analyze interaction of beta-sesquiphellandrene (compound belongs to ginger) with spike protein (Sp) and membrane glycoprotein polyprotein (MPp). Results Our molecular docking and simulation study reveals the perfect binding pocket of Sp and MPp holding beta-sesquiphellandrene (bS). Binding energies for MPp-bS and Sp-bS were found to be − 9.5 kcal/mol and − 10.3 kcal/mol respectively. RMSD and RMSF values for docked complexes were found to be in selectable range, i.e., 1 to 3 Å and 1 to 8 Å respectively. Modern computational tools were used here to make this investigation fast and effective. Further, ADME analysis reveals the therapeutic validations for beta-sesquiphellandrene to act as a useful pharmacoactive compound. Beta-sesquiphellandrene provides not only inhibitory effect on spike protein of SARS-CoV2 but also similar inhibitory effects on membrane glycoprotein polyprotein complex of SFTS virus, which hampers the pathological initiation of the diseases caused by both the viruses, i.e., COVID-19 and severe fever with thrombocytopenia syndrome. Conclusion This method of computational analysis was found to be rapid and effective, and opens new doors in the domain of in silico drug discovery. Beta-sesquiphellandrene can be used as effective medicine to control these harmful pathogens after wet lab validations.

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“…The patient died of disseminated intravascular coagulation. The sustained tick bite provided the extended opportunity to inject viruses into the wound, allowing these to enter the blood stream, and spread to the organs and tissues for replication [14], thereby elevating the serum virus load. Since there is no direct antiviral treatment for SFTS, the physical protection of tick bites represent an important measure to prevent the transmission and infection of SFTSV.…”

Section: Discussionmentioning

confidence: 99%

Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China

Tong¹,

Wang

et al. 2020

Virol J

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Background: Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient's serum to establish a solid pathogen diagnosis. Case presentation: We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient's abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient's serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. Conclusion: The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.

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

Cited by 65 publications

References 57 publications

Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite

Pathological Characteristics of a Patient with Severe Fever with Thrombocytopenia Syndrome (SFTS) Infected with SFTS Virus through a Sick Cat’s Bite

Molecular docking and simulation investigation: effect of beta-sesquiphellandrene with ionic integration on SARS-CoV2 and SFTS viruses

Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China

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