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:Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne infectious disease caused by a new SFTS virus (SFTSV). Due to its 12%-50% high fatality rate and the possibility of pandemic transmission, as well as no specific antiviral drugs for the treatment so far, SFTSV has been listed as one of the top 10 priority infectious diseases by the World Health Organization. Currently, there are rare studies of transcriptomic analysis for the patients infected with SFTSV, which makes it difficult to deeply understand the life cyle and pathogenicity of this virus. To explore the differences of transcripts after SFTSV infection, we performed a longitudinal sampling study to systematically investigate the chronological changes of viral load and transcriptomic and epigenetic characterization using white blood cells from SFTSV patients. The results showed significant changes in the expression of some genes from onset to recovery of SFTSV infection. Moreover, these differentially expressed genes showed good consistency in the three patients at different stages of treatment, which may contribute to the pathophysiology of SFTSV and thus lead to a breakthrough in SFTSV therapy. Moreover, by m6A-seq, we found some genes that might be regulated by m6A. This study in transcript changes and RNA modification may open a brand new direction to our understanding of SFTSV and play an important role in the drugs discovery for effective treatment.
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:We infect bone marrow derived macrophages (BMDMs) with either a Hyper or Hypovirulent Mycobacterium tuberculolsis strain and assess the host response to these bacteria through RNAseq Uninfected BMDMs served as controls, BMDMs infected with Hypervirulent M.tb (designated R55), BMDMs infected with Hypovirulent m.tb (designated R50). 3 groups with 3 biological replicates, each analysed in triplicate.
Project description:We infect bone marrow derived macrophages (BMDMs) with Mycobacterium cultured with and without Tween 80 and asses the host response to these bacteria through RNAseq Uninfected BMDMs served as controls, BMDMs infected with detergent-free M.tb (designated RNT), BMDMs infected with Tween cultured m.tb (designated RT). 3 groups with 3 biological replicates, each analysed in triplicate.
Project description:To explore the spatiotemporal regulation of ASC speck formation and inflammasome activation, we infected primary WT and Asc–/– bone marrow-derived macrophages (BMDMs) with the bacterium Francisella novicida to induce AIM2 inflammasome activation and then performed ASC IP-MS to identify proteins that interacted with ASC. We compared the IP products between WT BMDMs and Asc–/– BMDMs, and found that many proteins specifically interacted with ASC.
2024-05-29 | PXD052497 | Pride
Project description:RNA-seq of SFTSV infected THP-1 cells