单纯疱疹病毒Ⅰ型基因突变株M3株与水痘带状疱疹病毒减毒活疫苗Oka株感染小鼠的生物学特性比较
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摘要
目的比较单纯疱疹病毒Ⅰ型(herpes simplex virus typeⅠ,HSV-Ⅰ)基因突变株M3株与水痘带状疱疹病毒(varicella-zoster virus,VZV)减毒活疫苗Oka株感染BALB/c小鼠的生物学特性。方法用不同剂量(103、104、105 PFU/只)的HSV-ⅠM3株及疫苗剂量的VZV Oka株以不同方式(腹腔、肌肉、鼻腔、足垫)感染小鼠后,对小鼠的急性临床反应、体重变化、病毒增殖、组织病理损伤及病毒重激活等生物学特性进行比较。结果 HSV-ⅠM3及VZV Oka组小鼠均未见弓背、倒毛、单侧眼失明等急性临床症状,体重均呈逐渐上升趋势;器官组织中病毒拷贝数均处于较低水平,且两组差异无统计学意义(P> 0. 05);小鼠脑组织出现轻微局部炎症细胞浸润、出血、胶质小结或无异常,两组差异较小,脊髓组织均未出现明显异常;神经组织与Vero细胞共培养,均未观察到细胞病变(CPE)。结论 HSV-ⅠM3株与VZV Oka株感染小鼠后的生物学特征无明显差异。
Objective To compare the biological characteristics of BALB/c mice infected with herpes simplex virus type-Ⅰ(HSV-Ⅰ)mutant strain M3 and live attenuated varicella-zoster virus(VZV)vaccine Oka strain. Methods Mice were infected with HSV-ⅠM3 strain at various dosages(103,104 and 105 PFU)and VZV Oka strain at vaccine dosage respectively by various(intraperitoneal,intramuscular,nasal and foot pad)routes,of which the biological characteristics such as acute clinical reaction,body weight,virus proliferation,histopathologic lesion and virus reactivation were compared.Results No obvious clinical symptoms of acute reactions such as dorsal bow,inverted hair and blindness of unilateral eye were observed in the mice in HSV-ⅠM3 and VZV Oka groups,while the bodyweights increased gradually. The virus copy numbers in organ and tissue of mice in HSV-ⅠM3 and VZV Oka groups were small,which showed no significant difference(P > 0. 05).The brain tissue of mice showed mild local inflammatory cell infiltration,hemorrhage,colloidal nodule or no abnormality,which showed little difference in HSV-ⅠM3 and VZV Oka groups. However,no obvious abnormalities were observed in spinal cord tissue of various groups. No CPE was observed in the co-culture of nerve tissue and Vero cells. Conclusion The biological characteristics of mice infected with HSV-ⅠM3 strain and VZV Oka strain showed no significant difference.
Objective To compare the biological characteristics of BALB/c mice infected with herpes simplex virus type-Ⅰ(HSV-Ⅰ)mutant strain M3 and live attenuated varicella-zoster virus(VZV)vaccine Oka strain. Methods Mice were infected with HSV-ⅠM3 strain at various dosages(103,104 and 105 PFU)and VZV Oka strain at vaccine dosage respectively by various(intraperitoneal,intramuscular,nasal and foot pad)routes,of which the biological characteristics such as acute clinical reaction,body weight,virus proliferation,histopathologic lesion and virus reactivation were compared.Results No obvious clinical symptoms of acute reactions such as dorsal bow,inverted hair and blindness of unilateral eye were observed in the mice in HSV-ⅠM3 and VZV Oka groups,while the bodyweights increased gradually. The virus copy numbers in organ and tissue of mice in HSV-ⅠM3 and VZV Oka groups were small,which showed no significant difference(P > 0. 05).The brain tissue of mice showed mild local inflammatory cell infiltration,hemorrhage,colloidal nodule or no abnormality,which showed little difference in HSV-ⅠM3 and VZV Oka groups. However,no obvious abnormalities were observed in spinal cord tissue of various groups. No CPE was observed in the co-culture of nerve tissue and Vero cells. Conclusion The biological characteristics of mice infected with HSV-ⅠM3 strain and VZV Oka strain showed no significant difference.
引文
[1]LEMMEDU P G E,ROVNAK L J,HUSSAIN B,et al.A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation[J].J Gen Virol,2015,96:1581-1602.
[2]ZUCKERMAN R A,LIMAYE A P.Varicella zoster virus(VZV)and herpes simplex virus(HSV)in solid organ transplant patients[J].Am J Transplant,2013,13:55-66.
[3]LIEDTKE W,OPALKA B,et al.Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue[J].Neurol Sci,1993,116(1):6-11.
[4]EGAN K P,WU S,WIGDAHL B,JENNINGS SR.Immunological control of herpes simplex virus infections[J].Neurovirol,2013,19(4):328-345.
[5]TANG H M,JIA J L,YAO K.Latent infection of varicellazoster virus[J].J Microbes Infect,2016,11(6):374-379.(in Chinese)汤华民,贾俊丽,姚堃.水痘-带状疱疹病毒潜伏感染的研究现状[J].微生物与感染,2016,11(6):374-379.
[6]GERSHON A A.Varicella zoster vaccines and their implications for development of HSV vaccines[J].Virology,2013,435(1):29-36.
[7]AWASTHI S,FRIDEMAN H M.Status of prophylactic and therapeutic genital herpes vaccines[J].Curr Opin Virol,2014,6:6-12.
[8]XU X L,FAN S T,WANG X,et al.Analysis of the protective immunity induced by herpes simplex virus 1 strain M3 with an attenuated phenotype due to mutations in the viral ul7,ul41,and LAT genes[J].Front Microbiol,2017,8:1958.
[9]XU X L,GUO Y Q,FAN S T,et al.Attenuated phenotypes and analysis of a herpes simplex virus 1strain with partial deletion of the UL7,UL41 and LAT genes[J].Virologica Sinica,2017,32(5):404-414.
[10]LI Y C,GAO Z G,TAO H,et al.Safety of freeze-dried live attenuated varicella vaccine[J].Chin J Biologicals,2012,25(12):1667-1670.(in Chinese)李永成,高志刚,陶航,等.冻干水痘减毒活疫苗的安全性评价[J].中国生物制品学杂志,2012,25(12):1667-1670.
[11]MITRA M,FARIDI M,GHOSH A,et al.Safety and immunogenicity of single dose live attenuated varicella vaccine(VR 795Oka strain)in healthy Indian children:a randomized con-trolled study[J].Hum Vacc&Immunother,2015,11(2):443-449.
[12]HABERTHUR K,MESSAOUDI I.Animal models of varicella zoster virus infection[J].Pathogens,2013,2:364-382.
[13]LI Z J,LI J Q,ZHANG Y.Varicella-animal model of herpes zoster infection[J].Foreign Med Virol,2001,21(2):118-121.(in Chinese)李振洁,李际强,张毅.水痘-带状疱疹病毒感染的动物模型[J].国外医学病毒学分册,2001,21(2):118-121.
[14]TANG B B,ZHANG X L,HE Y F,et al.Differences in clinical,pathological and etiological features of herpes simplex virus 1infection in different BALB/c mouse models[J].Chin J Microbiol Immunol,2017,37(3):200-207.(in Chinese)汤贝贝,张小龙,何玉凤,等.BALB/c小鼠在HSV-Ⅰ不同条件感染下的临床与病理及病原差异分析[J].中华微生物学和免疫学杂志,2017,37(3):200-207.
[15]HE Y F,ZHANG Y,XU X L,et al.Comparative analysis on infectious features between HSV-1 mutants strain M3 and its wildtype strain Mckera[J].Chin J Viral Dis,2017,7(6):412-419.(in Chinese)何玉凤,张勇,徐兴丽,等.单纯疱疹病毒Ⅰ型基因修饰突变株M3与野生型毒株Mckrae感染特征的比较分析[J].中国病毒病杂志,2017,7(6):412-419.
[16]ZHANG X L,JIANG Q L,XU X L,et al.Immune mechanismsinduced by an HSV-Ⅰmutant strain:discrepancy analysis of the immune system gene profile in comparison with a wildtype strain[J].Vaccine,2018(36):2394-2402.
[17]XU X L,FAN S T,ZHOU J N,et al.The mutated tegument protein UL7 attenuates the virulence of herpes simplex virus 1by reducing the modulation ofα-4 gene transcription[J].Virol J,2016,13:152.
[2]ZUCKERMAN R A,LIMAYE A P.Varicella zoster virus(VZV)and herpes simplex virus(HSV)in solid organ transplant patients[J].Am J Transplant,2013,13:55-66.
[3]LIEDTKE W,OPALKA B,et al.Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue[J].Neurol Sci,1993,116(1):6-11.
[4]EGAN K P,WU S,WIGDAHL B,JENNINGS SR.Immunological control of herpes simplex virus infections[J].Neurovirol,2013,19(4):328-345.
[5]TANG H M,JIA J L,YAO K.Latent infection of varicellazoster virus[J].J Microbes Infect,2016,11(6):374-379.(in Chinese)汤华民,贾俊丽,姚堃.水痘-带状疱疹病毒潜伏感染的研究现状[J].微生物与感染,2016,11(6):374-379.
[6]GERSHON A A.Varicella zoster vaccines and their implications for development of HSV vaccines[J].Virology,2013,435(1):29-36.
[7]AWASTHI S,FRIDEMAN H M.Status of prophylactic and therapeutic genital herpes vaccines[J].Curr Opin Virol,2014,6:6-12.
[8]XU X L,FAN S T,WANG X,et al.Analysis of the protective immunity induced by herpes simplex virus 1 strain M3 with an attenuated phenotype due to mutations in the viral ul7,ul41,and LAT genes[J].Front Microbiol,2017,8:1958.
[9]XU X L,GUO Y Q,FAN S T,et al.Attenuated phenotypes and analysis of a herpes simplex virus 1strain with partial deletion of the UL7,UL41 and LAT genes[J].Virologica Sinica,2017,32(5):404-414.
[10]LI Y C,GAO Z G,TAO H,et al.Safety of freeze-dried live attenuated varicella vaccine[J].Chin J Biologicals,2012,25(12):1667-1670.(in Chinese)李永成,高志刚,陶航,等.冻干水痘减毒活疫苗的安全性评价[J].中国生物制品学杂志,2012,25(12):1667-1670.
[11]MITRA M,FARIDI M,GHOSH A,et al.Safety and immunogenicity of single dose live attenuated varicella vaccine(VR 795Oka strain)in healthy Indian children:a randomized con-trolled study[J].Hum Vacc&Immunother,2015,11(2):443-449.
[12]HABERTHUR K,MESSAOUDI I.Animal models of varicella zoster virus infection[J].Pathogens,2013,2:364-382.
[13]LI Z J,LI J Q,ZHANG Y.Varicella-animal model of herpes zoster infection[J].Foreign Med Virol,2001,21(2):118-121.(in Chinese)李振洁,李际强,张毅.水痘-带状疱疹病毒感染的动物模型[J].国外医学病毒学分册,2001,21(2):118-121.
[14]TANG B B,ZHANG X L,HE Y F,et al.Differences in clinical,pathological and etiological features of herpes simplex virus 1infection in different BALB/c mouse models[J].Chin J Microbiol Immunol,2017,37(3):200-207.(in Chinese)汤贝贝,张小龙,何玉凤,等.BALB/c小鼠在HSV-Ⅰ不同条件感染下的临床与病理及病原差异分析[J].中华微生物学和免疫学杂志,2017,37(3):200-207.
[15]HE Y F,ZHANG Y,XU X L,et al.Comparative analysis on infectious features between HSV-1 mutants strain M3 and its wildtype strain Mckera[J].Chin J Viral Dis,2017,7(6):412-419.(in Chinese)何玉凤,张勇,徐兴丽,等.单纯疱疹病毒Ⅰ型基因修饰突变株M3与野生型毒株Mckrae感染特征的比较分析[J].中国病毒病杂志,2017,7(6):412-419.
[16]ZHANG X L,JIANG Q L,XU X L,et al.Immune mechanismsinduced by an HSV-Ⅰmutant strain:discrepancy analysis of the immune system gene profile in comparison with a wildtype strain[J].Vaccine,2018(36):2394-2402.
[17]XU X L,FAN S T,ZHOU J N,et al.The mutated tegument protein UL7 attenuates the virulence of herpes simplex virus 1by reducing the modulation ofα-4 gene transcription[J].Virol J,2016,13:152.