The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccin...The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccination in children,the incidence among older individuals has increased substantially.Despite this epidemiological shift,research on JEV infection in the elderly remains limited.We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms.Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types.To further characterize immune response variations,we conducted transcriptomic sequencing on the brain tissues following JEV infection.Aged mice exhibited lower mortality,delayed disease progression,and milder brain pathology compared to young mice after JEV infection.Viral titers and infection rates of major brain cell types were similar in both groups.Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice.Additionally,microglial activation and CD8^(+) T cell function were significantly reduced.Interestingly,JEV infection induced the selective recruitment of B cells in the brains of aged mice.These B cells may modulate the effects of CD8^(+) T cells in the disease process.Compared to young mice,aged mice showed enhanced resistance to JEV progression and reduced brain pathology.This resistance was associated with a weakened immune response in the aged brain,rather than differences in viral infection.The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.展开更多
As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)...As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)secretion,growth delay and deficits in learning and memory in suckling mice.Early administration of GH can improve the cognitive function of the mice.Therefore,in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice.Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication.Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.展开更多
Zika virus(ZIKV)poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage.However,deficiency of human testicular samples hinders the in-depth research ...Zika virus(ZIKV)poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage.However,deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury.Organoids are relatively simple in vitro models,which could mimic the pathological changes of corresponding organs.In this study,we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice.Similar to the testis,this organoid system has a blood-testis barrier(BTB)-like structure and could synthesize testosterone.ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis.Therefore,our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.展开更多
基金the National Natural Science Foundation of China(82172266to P.G.W.)Natural Science Foundation of Beijing(7232002 to N.G.).
文摘The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccination in children,the incidence among older individuals has increased substantially.Despite this epidemiological shift,research on JEV infection in the elderly remains limited.We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms.Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types.To further characterize immune response variations,we conducted transcriptomic sequencing on the brain tissues following JEV infection.Aged mice exhibited lower mortality,delayed disease progression,and milder brain pathology compared to young mice after JEV infection.Viral titers and infection rates of major brain cell types were similar in both groups.Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice.Additionally,microglial activation and CD8^(+) T cell function were significantly reduced.Interestingly,JEV infection induced the selective recruitment of B cells in the brains of aged mice.These B cells may modulate the effects of CD8^(+) T cells in the disease process.Compared to young mice,aged mice showed enhanced resistance to JEV progression and reduced brain pathology.This resistance was associated with a weakened immune response in the aged brain,rather than differences in viral infection.The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.
基金the grants from the National Key Research and Development Plan of China(2021YFC2300200)the National Natural Science Foundation of China(NSFC)(U1902210 and 81972979 to J.An,and 82172266 to P.G.Wang)Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Fiveyear Plan(IDHT20190510 to J.An)。
文摘As a member of vector-borne viruses,Zika virus(ZIKV)can cause microcephaly and various neurological symptoms in newborns.Previously,we found that ZIKV could infect hypothalamus,causing a decrease in growth hormone(GH)secretion,growth delay and deficits in learning and memory in suckling mice.Early administration of GH can improve the cognitive function of the mice.Therefore,in this study we further investigated the mechanism underlying the protective role of GH in ZIKV infection in suckling mice.Our results showed that GH could effectively reduce brain damage caused by ZIKV infection via reducing cell apoptosis and inflammatory response rather than inhibiting viral replication.Our results provide important evidences not only for understanding the mechanism underlying ZIKV-associated neurological symptoms but also for the treatment of ZIKV infection.
基金funded by the National Key Research and Development Plan of China(2021YFC2300202)the National Natural Science Foundation of China(U1902210,81871641,81972979,82172266,81902048)+1 种基金the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(IDHT20190510)the Beijing Key Laboratory of Emerging Infectious Diseases(NO.DTKF202103).
文摘Zika virus(ZIKV)poses a serious threat to global public health due to its close relationship with neurological and male reproductive damage.However,deficiency of human testicular samples hinders the in-depth research on ZIKV-induced male reproductive system injury.Organoids are relatively simple in vitro models,which could mimic the pathological changes of corresponding organs.In this study,we constructed a 3D testicular organoid model using primary testicular cells from adult BALB/c mice.Similar to the testis,this organoid system has a blood-testis barrier(BTB)-like structure and could synthesize testosterone.ZIKV tropism of testicular cells and ZIKV-induced pathological changes in testicular organoid was also similar to that in mammalian testis.Therefore,our results provide a simple and reproducible in vitro testicular model for the investigations of ZIKV-induced testicular injury.
