BIOLOGICAL CHARACTERIZATION OF RECOMBINANT VACCINIA VIRUSES IN MICE INFECTED BY THE RESPIRATORY ROUTE

被引:104
作者
WILLIAMSON, JD [1 ]
REITH, RW [1 ]
JEFFREY, LJ [1 ]
ARRAND, JR [1 ]
MACKETT, M [1 ]
机构
[1] CHRISTIE HOSP & HOLT RADIUM INST,PATERSON INST CANC RES,CANC RES CAMPAIGN LABS,MANCHESTER M20 9BX,LANCS,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1099/0022-1317-71-11-2761
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A murine model based on infection by the respiratory route has been used to study the pathogenesis of recombinant vaccinia viruses. The neurovirulent Western Reserve (WR) strain and the Wyeth smallpox vaccine strain were used as vectors. Recombinant viruses were constructed by insertion of the Epstein-Barr virus membrane glycoprotein 340 gene into the thymidine kinase (TK) gene of each vaccinia virus. Intranasal inoculation of DBA/2 mice with 106 pockforming units (pk.f.u.) of the WR strain was lethal but mice survived similar infection with the WR recombinant virus. Each virus was recovered from lung, blood and brain but, unlike wild-type virus, the recombinant virus was subsequently cleared. No deaths occurred after similar infection with the Wyeth strain or the Wyeth recombinant virus. There was limited growth of the Wyeth strain in the respiratory tract, low levels of virus in the blood and only sporadic recovery in brain extracts. The Wyeth recombinant virus was cleared rapidly with little viraemia or detectable infection of the central nervous system. No phenotypic character determined in vitro could be related consistently to the virulence of wild-type and recombinant viruses. Although the lethal character of the WR strain was affected by its TK+ phenotype, mice survived infection by intranasal inoculation with 106 pk.f.u. of WR TK+ recombinant viruses which either expressed the human interleukin 2 gene or had a deficient vaccinia virus growth factor gene.
引用
收藏
页码:2761 / 2767
页数:7
相关论文
共 44 条
[1]   POSSIBLE RELATION BETWEEN HUMAN PATHOGENICITY OF SMALLPOX VACCINES AND VIRUS GROWTH AT ELEVATED-TEMPERATURES [J].
BAXBY, D .
JOURNAL OF HYGIENE, 1974, 73 (01) :35-37
[2]  
BAXBY D, 1975, PROG MED VIROL, V19, P215
[3]  
BAXBY D, 1986, LANCET, V2, P850
[4]   ORAL VACCINATION OF THE FOX AGAINST RABIES USING A LIVE RECOMBINANT VACCINIA VIRUS [J].
BLANCOU, J ;
KIENY, MP ;
LATHE, R ;
LECOCQ, JP ;
PASTORET, PP ;
SOULEBOT, JP ;
DESMETTRE, P .
NATURE, 1986, 322 (6077) :373-375
[5]  
Boulter E A, 1973, Prog Med Virol, V16, P86
[6]   NON-ESSENTIAL GENES IN THE VACCINIA VIRUS HINDIII K-FRAGMENT - A GENE RELATED TO SERINE PROTEASE INHIBITORS AND A GENE RELATED TO THE K-37 VACCINIA VIRUS MAJOR ENVELOPE ANTIGEN [J].
BOURSNELL, MEG ;
FOULDS, IJ ;
CAMPBELL, JI ;
BINNS, MM .
JOURNAL OF GENERAL VIROLOGY, 1988, 69 :2995-3003
[7]   RESPONSE OF MICE TO ECTROMELIA AND VACCINIA VIRUSES [J].
BRIODY, BA .
BACTERIOLOGICAL REVIEWS, 1959, 23 (02) :61-95
[8]  
BROWN F, 1990, LANCET, V1, P587
[9]   DELETION OF THE VACCINIA VIRUS GROWTH-FACTOR GENE REDUCES VIRUS VIRULENCE [J].
BULLER, RML ;
CHAKRABARTI, S ;
COOPER, JA ;
TWARDZIK, DR ;
MOSS, B .
JOURNAL OF VIROLOGY, 1988, 62 (03) :866-874
[10]   DECREASED VIRULENCE OF RECOMBINANT VACCINIA VIRUS EXPRESSION VECTORS IS ASSOCIATED WITH A THYMIDINE KINASE-NEGATIVE PHENOTYPE [J].
BULLER, RML ;
SMITH, GL ;
CREMER, K ;
NOTKINS, AL ;
MOSS, B .
NATURE, 1985, 317 (6040) :813-815