Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studie...Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studies on IFITM3,particularly those focused on innate antiviral defense mechanisms,have shown that IFITM3 affects the body’s adaptive immune response.The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics,flow cytometry,and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK)cell numbers,their activation,and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice.Moreover,the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results,we speculate that the NK cells are more readily activated in the absence of IFITM3,increasing mortality in Ifitm3-/-mice.展开更多
Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candi...Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.展开更多
Acute respiratory infections are the most common illnesses experienced by people of all ages worldwide.Previous epidemiologic studies have shown that viruses cause most of these acute respiratory illnesses[1].
基金supported by the National Science Fund for Distinguished Young Scholars of China[Grant No.81525017]National Natural Youth Science Foundation[Grant No.31900140]。
文摘Objective Interferon-induced transmembrane protein 3(IFITM3)is an important member of the IFITM family.However,the molecular mechanisms underlying its antiviral action have not been completely elucidated.Recent studies on IFITM3,particularly those focused on innate antiviral defense mechanisms,have shown that IFITM3 affects the body’s adaptive immune response.The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics,flow cytometry,and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK)cell numbers,their activation,and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice.Moreover,the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results,we speculate that the NK cells are more readily activated in the absence of IFITM3,increasing mortality in Ifitm3-/-mice.
基金This study was supported by the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China[No.2018ZX10711001,2018ZX10305409-004-002]Emergency Prevention and Control Project of Ministry of Science and Technology of China[No.10600100000015001206].
文摘Objective In China, 24 cases of human infection with highly pathogenic avian influenza(HPAI) H5 N6 virus have been confirmed since the first confirmed case in 2014. Therefore, we developed and assessed two H5 N6 candidate vaccine viruses(CVVs).Methods In accordance with the World Health Organization(WHO) recommendations, we constructed two reassortant viruses using reverse genetics(RG) technology to match the two different epidemic H5 N6 viruses. We performed complete genome sequencing to determine the genetic stability. We assessed the growth ability of the studied viruses in MDCK cells and conducted a hemagglutination inhibition assay to analyze their antigenicity. Pathogenicity attenuation was also evaluated in vitro and in vivo.Results The results showed that no mutations occurred in hemagglutinin or neuraminidase, and both CVVs retained their original antigenicity. The replication capacity of the two CVVs reached a level similar to that of A/Puerto Rico/8/34 in MDCK cells. The two CVVs showed low pathogenicity in vitro and in vivo, which are in line with the WHO requirements for CVVs.Conclusion We obtained two genetically stable CVVs of HPAI H5N6 with high growth characteristics,which may aid in our preparedness for a potential H5N6 pandemic.
基金supported by the National Mega-projects for Infectious Diseases,P.R.China[grant numbers 2018ZX10201002-008-001 and 2018ZX10201002-008-004]the General Program of the National Natural Science Foundation of China[82041041]
文摘Acute respiratory infections are the most common illnesses experienced by people of all ages worldwide.Previous epidemiologic studies have shown that viruses cause most of these acute respiratory illnesses[1].