The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease.animal model | phlebovirus | pathology | reduction of platelets | macrophage infection S evere fever with thrombocytopenia syndrome (SFTS) is a recently identified emerging viral infectious disease in China that is caused by a novel phlebovirus in the family Bunyaviridae, SFTS virus (SFTSV) (1). Clinical features of SFTS patients include abrupt high fever, thrombocytopenia, leukocytopenia, and gastrointestinal symptoms. Laboratory tests commonly show elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactate dehydrogenase, creatine kinase, creatine kinase MB fraction, as well as elongated activated partial-thromboplastin time (1). These abnormally changed laboratory parameters are indicative of the pathological lesions that occur in multiple organs and altered homeostasis of the coagulation systems of SFTS patients. Pathological studies of SFTS are absent because patient tissues are rarely donated after death in rural areas of China. Therefore, the causes of illness and death, as well as pathological changes within organs, remain unclear. To systematically investigate the pathogenic mechanisms of SFTS and understand key symptoms, such as thrombocytopenia, infectious animal models for SFTSV are urgently needed. ResultsEstablishment of a SFTSV Pathogenic Mouse Model. In our initial study, to identify an infectious animal model that could mimic most clinical features during SFTSV infection, the susceptibilities of three commonly used laboratory rodent strains for phlebovirus (2-4), C57/BL6 mice, BalB/C mice, and Syrian hamsters, were examined. The SFTSV strain HB29 was inoculated at 10 5 TCID 50 (50% tissue culture infective dose) per mouse or 5 × 10 5 TCID 50 per hamster through four different routes of infection, including intravenous, intramuscular, intraperitoneal, and intracerebral...

BackgroundThe development of new therapeutic targets and strategies to control highly pathogenic avian influenza (HPAI) H5N1 virus infection in humans is urgently needed. Broadly cross-neutralizing recombinant human antibodies obtained from the survivors of H5N1 avian influenza provide an important role in immunotherapy for human H5N1 virus infection and definition of the critical epitopes for vaccine development.Methodology/Principal FindingsWe have characterized two recombinant baculovirus-expressed human antibodies (rhAbs), AVFluIgG01 and AVFluIgG03, generated by screening a Fab antibody phage library derived from a patient recovered from infection with a highly pathogenic avian influenza A H5N1 clade 2.3 virus. AVFluIgG01 cross-neutralized the most of clade 0, clade 1, and clade 2 viruses tested, in contrast, AVFluIgG03 only neutralized clade 2 viruses. Passive immunization of mice with either AVFluIgG01 or AVFluIgG03 antibody resulted in protection from a lethal H5N1 clade 2.3 virus infection. Furthermore, through epitope mapping, we identify two distinct epitopes on H5 HA molecule recognized by these rhAbs and demonstrate their potential to protect against a lethal H5N1 virus infection in a mouse model.Conclusions/SignificanceImportantly, localization of the epitopes recognized by these two neutralizing and protective antibodies has provided, for the first time, insight into the human antibody responses to H5N1 viruses which contribute to the H5 immunity in the recovered patient. These results highlight the potential of a rhAbs treatment strategy for human H5N1 virus infection and provide new insight for the development of effective H5N1 pandemic vaccines.

This study aims to effectively solve the problem of the destruction of the coal roof and floor overlying rock after mining the protective layer, and determines whether the gas in the protected layer can be effectively released. We do this based on the engineering background of the Weng’an Coal Mine; research and analysis of the movement of the roof and floor overlying rocks; the evolution of cracks and the pressure relief characteristics of the protected layer after mining the protective layer; and through theoretical analysis and similar simulation experiments. Through numerical simulation, it was found that the protected layer was depressurized due to the mining of the protective layer, and the decompression rate of the protected layer was 0.2–0.8. In addition, the overall expansion rate of the protected layer was greater than the requirements of the “Detailed Rules for Prevention and Control of Coal and Gas Outbursts” for coal mines, and the investigation of the residual gas pressure and content of the protected layer revealed that the protected coal seam had been mined in the upper protective layer coal face. The gas pressure dropped to 50.7% of the original coal seam gas pressure, the rate of decrease was 49.3%, the residual gas content dropped by 68.67%, and the gas concentration in the return airway was 0.31% on average, meeting the national regulations that require its value to be less than or equal to 1%. The study comprehensively demonstrates that mining of the protective layer is beneficial to the release of gas from the protected layer, and provides a practical reference for coal and gas outbursts in mines.