Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases,including herpes simplex encephalitis and meningitis.According to recent studies,PNKP significantly affects ...Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases,including herpes simplex encephalitis and meningitis.According to recent studies,PNKP significantly affects the proliferation of HSV-1 in astrocytes.Here,we used viral proliferation curves to confirm the significant inhibitory effects of PNKP on HSV-1 proliferation.PNKP downregulation was also confirmed by analyzing the transcription of viral genes.We found that PNKP downregulation affects the viral DNA copy number.This study preliminarily confirms that PNKP affects viral proliferation by affecting HSV-1 genome cyclization.These results also suggest that astrocytes play a specific role in preventing HSV-1 infection.展开更多
Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involve...Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems.Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum.Besides,mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration.Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system.As models,we analyze PNKP-related disorders,focusing on Charcot-Marie-Tooth disease and ataxia.A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.展开更多
基金supported by the National Basic Research Program(2012CB518901)(China)National Natural Sciences Foundation of China(31100127)(China)the Yunnan Natural Science Foundation(2013FZ135,2013FZ128,2013FZ134)(China)
文摘Herpes simplex virus-1 (HSV-1) is a major pathogen that causes various central nervous system (CNS) diseases,including herpes simplex encephalitis and meningitis.According to recent studies,PNKP significantly affects the proliferation of HSV-1 in astrocytes.Here,we used viral proliferation curves to confirm the significant inhibitory effects of PNKP on HSV-1 proliferation.PNKP downregulation was also confirmed by analyzing the transcription of viral genes.We found that PNKP downregulation affects the viral DNA copy number.This study preliminarily confirms that PNKP affects viral proliferation by affecting HSV-1 genome cyclization.These results also suggest that astrocytes play a specific role in preventing HSV-1 infection.
基金Support from the University of Costa Rica is gratefully acknowledged(project 111-B2-372).
文摘Mutations in DNA repair enzymes can cause two neurological clinical manifestations:a developmental impairment and a degenerative disease.Polynucleotide kinase 3′-phosphatase(PNKP)is an enzyme that is actively involved in DNA repair in both single and double strand break repair systems.Mutations in this protein or others in the same pathway are responsible for a complex group of diseases with a broad clinical spectrum.Besides,mitochondrial dysfunction also has been consolidated as a hallmark of brain degeneration.Here we provide evidence that supports a shared role between mitochondrial dysfunction and DNA repair defects in the pathogenesis of the nervous system.As models,we analyze PNKP-related disorders,focusing on Charcot-Marie-Tooth disease and ataxia.A better understanding of the molecular dynamics of this relationship could provide improved diagnosis and treatment for neurological diseases.
