RECOMBINANTS BETWEEN ATTENUATED AND VIRULENT-STRAINS OF POLIOVIRUS TYPE-1 - DERIVATION AND CHARACTERIZATION OF RECOMBINANTS WITH CENTRALLY LOCATED CROSSOVER POINTS

RECOMBINANTS BETWEEN ATTENUATED AND VIRULENT-STRAINS OF POLIOVIRUS TYPE-1 - DERIVATION AND CHARACTERIZATION OF RECOMBINANTS WITH CENTRALLY LOCATED CROSSOVER POINTS
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DOI:
10.1016/0042-6822(85)90386-1
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发表时间:
1985-01-01
期刊:
影响因子:
3.7
通讯作者:
VIKTOROVA, EG
VIKTOROVA, EG
中科院分区:
医学3区
文献类型:
--
作者:
AGOL, VI;DROZDOV, SG;VIKTOROVA, EG

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从脊髓灰质炎病毒1型毒株和类型间(3型/1型)重组体的杂交中选择具有中心交叉点的重组子。对两个这样的重组子进行了详细的鉴定。在其中一株(v1/a1-6)中,基因组的5‘’半部分来自一株强毒1型毒株,而3‘’半株基因组来自一株弱毒1型毒株。另一个重组株(a1/v1-7)的基因组具有相反的结构,其5‘’和3‘’部分分别来自1型弱毒株和强毒株。从RNaseT1寡核苷酸图谱推断,A1/v1-7基因组也有一个相对较短的起源于脊髓灰质炎病毒3型的中心位置插入。两个重组子均表现为ts表型。重组子的RNA表型与捐献3‘’半基因组的亲本的表型相对应,分别表达RNA-和RNA+性状。尽管v1/a1-6是一种ts RNA病毒,但当它被注射到恒河猴的大脑中时,它被证明是神经毒力的,尽管与其强毒的1型亲本相比,它的致病性水平有所降低。重组A1/v1-7菌株表现为减毒株。这些数据支持了先前从脊髓灰质炎病毒重组体的实验中得出的结论,即脊髓灰质炎病毒的减毒表型在很大程度上取决于其基因组的5‘’半边的结构,尽管3‘’半边的突变可能在一定程度上减轻病毒的毒力。
Recombinants with a centrally located crossover point were selected from crosses between poliovirus type 1 strains and intertypic (type 3/type 1) recombinants. Two such recombinants were characterized in some detail. In one of them (v1/a1-6), the 5'' half of the genome was derived from a virulent type 1 strain, while the 3'' half came from an attenuated type 1 strain. The genome of the other recombinant (a1/v1-7) had the reverse organization, with the 5'' and 3'' halves being derived from the type 1 attenuated and virulent strains, respectively. As deduced from the RNase T1 oligonucleotide maps, the a1/v1-7 genome also had a relatively short centrally located insert of the poliovirus type 3 origin. Both recombinants exhibited ts phenotypes. The RNA phenotypes of the recombinants corresponded to that of the parent donating the 3'' half of the genome, v1/a1-6 and a1/v1-7 expressing RNA- and RNA+ characters, respectively. Despite being a ts RNA- virus, v1/a1-6 proved to be neurovirulent when injected intracerebrally into Cercopithecus aethiops monkeys, although it exhibited a somewhat diminished level of pathogenicity as compared to its virulent type 1 parent. Recombinant a1/v1-7 behaved as an attenuated strain. These data supported a previous conclusion drawn from the experiments with intertypic poliovirus recombinants that the attenuated phenotype of poliovirus depends largely on the structure of the 5'' half of its genome, although mutations of the 3'' half may alleviate the virulence of the virus to a degree.