Objective: This review aimed to summarize research progress regarding congenital cytomegalovirus (cCMV) infection-related nervous system diseases and their mechanisms. Data sources: All literature quoted in this review was retrieved from PubMed and Web of Science using the keywords "Cytomegalovirus" and "Neurologic disease" in English. To identify more important information, we did not set time limits. Study selection: Relevant articles were selected by carefully reading the titles and abstracts. Then, different diagnosis and clinical treatment methods for human CMV infection-related neurologic diseases were compared, and the main mechanism and pathogenesis of neurologic damage caused by CMV were summarized from the selected published articles. Results: cCMV infection is a major cause of neonatal malformation. cCMV can infect the fetal encephalon during early gestation and compromise neurodevelopment, resulting in varying degrees of neurologic damage, mainly including hearing impairment, central nervous system (CNS) infection, neurodevelopmental disorders, ophthalmic complications, cerebral neoplasms, infantile autism, epilepsy, and other neurologic abnormalities. Conclusions: cCMV infection-induced neurodevelopmental abnormalities, which were directly caused by fetal encephalon infection, thus inducing neuroimmune responses to damage nerve cells. Such abnormalities were also caused by suppression of the proliferation and differentiation of neural progenitor cells by CMV’s gene products. cCMV infection in the fetal encephalon can also inhibit neuronal migration and synapse formation and indirectly trigger placental inflammation and thus disrupt the oxygen supply to the fetus.
Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(MCMV)infection in BALB/c and C57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV.BALB/c and C57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.Contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of MCMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of MCMV infection.
