Human adenoviruses(HAdVs)are highly contagious pathogens with various genotypes implicated in acute respiratory disease(ARD)and linked to fatality,especially in immunosuppressed patients,young children,and military re...Human adenoviruses(HAdVs)are highly contagious pathogens with various genotypes implicated in acute respiratory disease(ARD)and linked to fatality,especially in immunosuppressed patients,young children,and military recruits.Currently,no vaccines or specific drugs are approved for clinical use.The hosts of adenoviruses are strictly species-specific,which strongly limits the development of vaccines and drugs against HAdVs.In this study,immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5(HAdV-5)via tail intravenous injection(i.v.).All mice challenged with a high dose of HAdV-5(3.21010 TCID50/kg)died within 3–5 days,while those receiving a low dose of HAdV-5(8109 or 4109 TCID50/kg)survived.Interestingly,among the mice receiving a medium dose of HAdV-5(1.61010 TCID50/kg),60%(n¼3/5)of male mice died,while all female mice survived.This suggests that male mice may be more susceptible to HAdV-5 infection than female mice,consistent with clinical findings in children.HAdV-5 DNA was mainly distributed in the liver,followed by the spleen and lung.Pathological changes were observed in the lung,liver,and spleen,with severity increasing in correlation with the virus challenge dosage.Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa,H2-Ea-ps,CD74,and H2-Eb1 genes in male mice,as well as the AHR gene in female mice,may contribute to the observed higher mortality rates in male mice.Therefore,this effective,feasible,and costefficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.展开更多
基金supported by grants from the National Natural Science Foundation of China(32170139 and 92269103)the R&D Program of Guangzhou Laboratory(No.SRPG22-006)+4 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515011190)the Science and Technology Program of Guangzhou,China(202201011115)the Open Foundation of Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University),Ministry of Education(2023VPPC-R07)China Postdoctoral Science Foundation(2023M731321)the Lifting Project Foundation of the Affiliated Guangdong Second Provincial General Hospital of Jinan University(TJGC-2022004).
文摘Human adenoviruses(HAdVs)are highly contagious pathogens with various genotypes implicated in acute respiratory disease(ARD)and linked to fatality,especially in immunosuppressed patients,young children,and military recruits.Currently,no vaccines or specific drugs are approved for clinical use.The hosts of adenoviruses are strictly species-specific,which strongly limits the development of vaccines and drugs against HAdVs.In this study,immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5(HAdV-5)via tail intravenous injection(i.v.).All mice challenged with a high dose of HAdV-5(3.21010 TCID50/kg)died within 3–5 days,while those receiving a low dose of HAdV-5(8109 or 4109 TCID50/kg)survived.Interestingly,among the mice receiving a medium dose of HAdV-5(1.61010 TCID50/kg),60%(n¼3/5)of male mice died,while all female mice survived.This suggests that male mice may be more susceptible to HAdV-5 infection than female mice,consistent with clinical findings in children.HAdV-5 DNA was mainly distributed in the liver,followed by the spleen and lung.Pathological changes were observed in the lung,liver,and spleen,with severity increasing in correlation with the virus challenge dosage.Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa,H2-Ea-ps,CD74,and H2-Eb1 genes in male mice,as well as the AHR gene in female mice,may contribute to the observed higher mortality rates in male mice.Therefore,this effective,feasible,and costefficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.
