Objective:To investigate the potential role of human cytomegalovirus lower matrix phosphoprotein 65(HCMV-pp65) in murine systemic lupus erythematosus(SLE).Methods:The prokaryotic plasmid pET-28b-pp65 was constructed t...Objective:To investigate the potential role of human cytomegalovirus lower matrix phosphoprotein 65(HCMV-pp65) in murine systemic lupus erythematosus(SLE).Methods:The prokaryotic plasmid pET-28b-pp65 was constructed to express the HCMVpp65 protein.BXSB mice and C57BL/6 mice were inoculated with pp65 eukarvotic plasmid pcDNA3.0-pp65 intramuscularly 5 times at 2-week intervals,and then the blood of the mice was subsequently collected via the retro-orbital vein.Indirect ELISAs were used to evaluate the concentration of anti-pp65 immunoglobulin G,anti-double-stranded DNA and antinuclear antibodies.lnterleukin-1β and tumor necrosis factor-α were also determined by competitive ELISA.At the same time,3 major SLE-related circulating microRNAs were examined by quantitative RT-PCR.Results:The early production of autoantibodies was observed in pp65-immunized male BXSB as well as C57BL/6 mice.Overexpression of interleukin-1β and tumor necrosis factor-a were detected in pp65-immunized male BXSB mice.Quantitative RT-PCR analyses showed that three SLE related microRNAs(microRNA-126,microRNA-125 a,and microRKA-146a) were dovvnrcgulatcd in peripheral blood mononuclear cells of pp65-immunizcd mice.Conclusions:Our findings indicate that HCMV-pp65 immunization strongly triggers the development and progression of" SLE-like disease in both BXSB and C57BL/6 mice,which indicates that the immune responses induced by HCMV-pp65 may be involved in the development of SLE.展开更多
Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger fo...Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.展开更多
基金Supported by National High Technology Research and Development Program of China(863 program No.2011AA02A116)
文摘Objective:To investigate the potential role of human cytomegalovirus lower matrix phosphoprotein 65(HCMV-pp65) in murine systemic lupus erythematosus(SLE).Methods:The prokaryotic plasmid pET-28b-pp65 was constructed to express the HCMVpp65 protein.BXSB mice and C57BL/6 mice were inoculated with pp65 eukarvotic plasmid pcDNA3.0-pp65 intramuscularly 5 times at 2-week intervals,and then the blood of the mice was subsequently collected via the retro-orbital vein.Indirect ELISAs were used to evaluate the concentration of anti-pp65 immunoglobulin G,anti-double-stranded DNA and antinuclear antibodies.lnterleukin-1β and tumor necrosis factor-α were also determined by competitive ELISA.At the same time,3 major SLE-related circulating microRNAs were examined by quantitative RT-PCR.Results:The early production of autoantibodies was observed in pp65-immunized male BXSB as well as C57BL/6 mice.Overexpression of interleukin-1β and tumor necrosis factor-a were detected in pp65-immunized male BXSB mice.Quantitative RT-PCR analyses showed that three SLE related microRNAs(microRNA-126,microRNA-125 a,and microRKA-146a) were dovvnrcgulatcd in peripheral blood mononuclear cells of pp65-immunizcd mice.Conclusions:Our findings indicate that HCMV-pp65 immunization strongly triggers the development and progression of" SLE-like disease in both BXSB and C57BL/6 mice,which indicates that the immune responses induced by HCMV-pp65 may be involved in the development of SLE.
基金supported by the following funds: the National Natural Science Foundation of China (81571275)the Beijing Municipal Natural Science Foundation (7144217)+5 种基金the Capital Applied Clinic Research Programs of Science and Technology (Z131107002213171)the Beijing Rising-star Plan of Science and Technology (Z141107001814042)the Open Research Fund of the Beijing Key Laboratory of Epilepsy Research (No. 2014DXBL02)Capital Medical University (15JL08)Scientific Research Common Program of Beijing Municipal Commission of Education (KM201610025001)Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (2014 1685)
文摘Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.
