Project description:Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus causing a high fatality of 12-50% in infected patients. In-depth understanding of the SFTSV induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics.
Project description:Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the WHO most dangerous pathogens, has 12-30% fatality rates with a characteristic thrombocytopenia syndrome. With a majority of clinically diagnosed SFTSV patients older than ~50 years, age is a critical risk factor for SFTSV morbidity and mortality. Here, we report an age-dependent ferret model of SFTSV infection and pathogenesis that fully recapitulates the clinical manifestations of human infections. While young adult ferrets (≤2 years old) did not show any clinical symptoms and mortality, SFTSV-infected aged ferrets (≥4 years old) demonstrated severe thrombocytopenia, reduced white blood cells, and high fever with 93% mortality rate. Moreover, significantly higher viral load was observed in aged ferrets. Transcriptome analysis of SFTSV-infected young ferrets revealed strong interferon-mediated anti-viral signaling, whereas inflammatory immune responses were markedly upregulated and persisted in aged ferrets. Thus, this immunocompetent age-dependent ferret model should be useful for anti-SFTSV therapy and vaccine development.
Project description:To investigate the response mechanisms of Severe fever with thrombocytopenia syndrome (SFTS) patients, we conducted transcriptomic analysis of peripheral immunity in 14 SFTS patients, ranging from modal infection to severe and fatal disease. Our results observed the potential mechanism for the heterogeneity of clinical symptoms, which can further elucidate the interaction between viruses and hosts and contribute to clinical treatment.
Project description:Dabie bandavirus, also termed as severe fever with thrombocytopenia syndrome virus (SFTSV), was first isolated in China in 2010. At this time, the virus was found to have spread to South Korea, Japan, and other countries. A high case fatality rate is reported for SFTS, ranging from 12–50% within various sources. Several omics for clinical studies among SFTS patients as well as studies of cultured SFTSV have attempted to characterize the relevant molecular biology and epidemiology of the disease. However, a global serum proteomics analysis among SFTS patients has not yet been reported to date. Thrombocytopenia and multiple organ failure are the major immediate causes of death among SFTS patients. In this study, serum proteomic changes related to thrombocytopenia, abnormal immune response, and inflammatory activation were documented in SFTS patients. These findings provide useful information forunderstanding the clinical manifestations of SFTS.
Project description:Typical symptoms of uncomplicated dengue fever (DF) include headache, muscle pains, rash, cough, and vomiting. A proportion of cases progress to severe dengue hemorrhagic fever (DHF), associated with vascular permeability, thrombocytopenia, and hemorrhages. Progression to severe dengue is difficult to diagnose at the onset of fever, which complicates patient triage, posing a socio-economic burden on health systems. To identify parameters associated with protection and susceptibility to DHF, we pursued a systems immunology approach integrating plasma chemokine profiling, high-dimensional mass cytometry and peripheral blood mononuclear cell transcriptomic analysis at the onset of fever in a prospective study conducted in Indonesia.
Project description:In order to determine the microRNAs profile in peripheral blood mononuclear cell (PBMC) from severe febrile with thrombocytopenia syndrome virus infection and investigate possible diagnostic value of these differential microRNAs.
