Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious...Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.展开更多
Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neuro...Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.展开更多
A mutant HSV(mtHSV) deleted icp34.5,an apoptosis-inhibiting gene w a s constructed. It is supposed that the mtHSV can replicate in p53-deficient cel l s selectively and lead to oncolysis targetedly. Mice tumor model h...A mutant HSV(mtHSV) deleted icp34.5,an apoptosis-inhibiting gene w a s constructed. It is supposed that the mtHSV can replicate in p53-deficient cel l s selectively and lead to oncolysis targetedly. Mice tumor model harboring sarco ma cell line s-180 was developed and the mtHSV was injected into the tumors. We found that the mean volume and weight of tumors of early therapeutic group(ETG) were reduced 49.29% and 38.31% of that of control tumors .In t he mid\|term group(MTG),the redutcion rate were 26.9% and 24.52% respectively.展开更多
文摘Oncolytic virus (OV) is a kind of virus that can preferentially infect and kill tumor cells. The second oncolytic virus drug was oncolytic herpes simplex virus (oHSV) Talimogene Laherparepvec (T-VEC). HSV-1 infectious cell culture protein 34.5 (ICP34.5) and latency-associated transcript (LAT) genes are closely related to virus selective infection and latent infection. Their engineering is essential for constructing efficient and safe oHSV. We summarized the mechanisms of ICP34.5 and LAT in the course of HSV-1 infection and reviewed the engineered oHSVs. We are aimed to provide an insight in developing oHSV in the future.
基金supported by grants from the National Natural Science Foundation of China-Yunnan Joint Found(NSFC,U2202215,U1602226)the National Natural Science Foundation of China(NSFC,81672040 to J.Zhou,8206306 to X.Cao,and 31802026 to L.Li)+11 种基金the Ministry of Science and Technology of China(MOST,2018YFC2000402,2018YFE0203700)the Ministry of Science and Technology of China Foreign Expert Program to J.Zhou(G2021061008L)the CAS“Light of West China”Program(xbzg-zdsys-201909)to J.Zhou,a Thousand Foreign Talent scholarship from Yunnan Province and High-end Foreign Expert Project of Yunnan Revitalization Talent Support Program to J.Zhouthe Technology Innovation Team of Kunming Medical University(CXTD201804)the International Science and Technology Cooperation Project(2017IB011)the Yunnan Training Project for Medical Talents(L-2017014)the biomedical Special Project of the Department of Science and Technology of Yunnan Province(202102AA100007-4)to X.Caothe Chinese Academy of Sciences President's International Fellowship Initiative(PIFI,2019VBA0045)to N.W.Fraserthe China Postdoctoral Science Foundation(2022MD713758)to E.Wangthe Medical reserve Talents Training Program of Yunnan Provincial Health Commission of China(H-2019059)to X.Huangthe Yunnan Fundamental Research Projects(202201AT070195)to Y.Ye.Open Research Fund HXDT-2019-1 to J.Zhou.
文摘Herpes simplex virus-1(HSV-1)is a widespread neurotropic virus that can reach the brain and cause a rare but acute herpes simplex encephalitis(HSE)with a high mortality rate.Most patients present with changes in neurological and behavioral status,and survivors suffer long-term neurological sequelae.To date,the pathogenesis leading to brain damage is still not well understood.HSV-1 induced encephalitis in the central nervous system(CNS)in animals are usually very diffuse and progressing rapidly,and mostly fatal,making the analysis difficult.Here,we established a mouse model of HSE via intracerebral inoculation of modified version of neuralattenuated strains of HSV-1(deletion of ICP34.5 and inserting a strong promoter into the latency-associated transcript region),in which the LMR-αΔpA strain initiated moderate productive infection,leading to strong host immune and inflammatory response characterized by persistent microglia activation.This viral replication activity and prolonged inflammatory response activated signaling pathways in neuronal damage,amyloidosis,Alzheimer's disease,and neurodegeneration,eventually leading to neuronal loss and behavioral changes characterized by hypokinesia.Our study reveals detailed pathogenic processes and persistent inflammatory responses in the CNS and provides a controlled,mild and non-lethal HSE model for studying long-term neuronal injury and increased risk of neurodegenerative diseases due to HSV-1 infection.
基金Supported by Foundation of86 3New Hi-technique Research(39880 0 31) Research Fund for the Doctoral Program m of Higher Educatio
文摘A mutant HSV(mtHSV) deleted icp34.5,an apoptosis-inhibiting gene w a s constructed. It is supposed that the mtHSV can replicate in p53-deficient cel l s selectively and lead to oncolysis targetedly. Mice tumor model harboring sarco ma cell line s-180 was developed and the mtHSV was injected into the tumors. We found that the mean volume and weight of tumors of early therapeutic group(ETG) were reduced 49.29% and 38.31% of that of control tumors .In t he mid\|term group(MTG),the redutcion rate were 26.9% and 24.52% respectively.
