Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes.
Partial dissociation of subgroup C phenotype and in vivo behaviour in feline leukaemia viruses with chimeric envelope genes.
复制标题
具有嵌合包膜基因的猫白血病病毒 C 亚型表型和体内行为的部分解离。
DOI：
10.1099/0022-1317-73-11-2839
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Neil,JC
中科院分区：
文献类型：
--
作者：
Rigby,MA;Rojko,JL;Stewart,MA;Kociba,GJ;Cheney,CM;Rezanka,LJ;Mathes,LE;Hartke,JR;Jarrett,O;Neil,JC
猫白血病病毒（FeLV）通过其在猫细胞上使用不同的宿主细胞受体（由病毒包膜决定的表型）分为A、B和C亚组。FeLV-A是FeLV的普遍存在的高感染性形式，FeLV-C分离株是罕见变异株，总是沿着FeLV-A分离。FeLV-C分离株具有诱导急性非再生性贫血的能力，原型FeLV-C/Sarma对猫具有强烈的年龄限制性感染性。FeLV-C/Sarmaenv序列与常见的弱致病性FeLV-A分离株密切相关。我们现在通过构建嵌合病毒表明，FeLV-A/格拉斯哥-1病毒的受体特异性可以通过交换单个可变结构域Vr 1而转化为FeLV-C的受体特异性，Vr 1的差异在于三个密码子缺失和九个相邻取代。试图通过定向诱变进一步分离该区域导致前病毒失能。独立的天然FeLV-C分离株的序列分析表明，它们具有独特的Vr 1序列，与保守的FeLV-A模式不同。获得FeLV-C的宿主范围和亚群特性的嵌合病毒保留了某些FeLV-A样特性，因为它们在3201 B猫T细胞中无细胞致病性，并且容易在断奶动物中诱导病毒血症。它们还在新生儿中诱导了严重贫血，其病程比FeLV-C/Sarma诱导的贫血更长，并且本质上是大红细胞性而非再生性。尽管受体特异性和致病性的主要决定因素与Vr 1分离，但似乎基因组中其他地方的序列独立于亚组表型影响感染性和致病性。
Feline leukaemia viruses (FeLVs) are classified into subgroups A, B and C by their use of different host cell receptors on feline cells, a phenotype which is determined by the viral envelope. FeLV-A is the ubiquitous, highly infectious form of FeLV, and FeLV-C isolates are rare variants which are invariably isolated along with FeLV-A. The FeLV-C isolates share the capacity to induce acute non-regenerative anaemia and the prototype, FeLV-C/Sarma, has strongly age-restricted infectivity for cats. The FeLV-C/Sarmaenvsequence is closely related to that of common, weakly pathogenic FeLV-A isolates. We now show by construction of chimeric viruses that the receptor specificity of FeLV-A/Glasgow-1 virus can be converted to that of FeLV-C by exchange of a singleenvvariable domain, Vr1, which differs by a three codon deletion and nine adjacent substitutions. Attempts to dissect this region further by directed mutagenesis resulted in disabled proviruses. Sequence analysis of independent natural FeLV-C isolates showed that they have unique Vr1 sequences which are distinct from the conserved FeLV-A pattern. The chimeric viruses which acquired the host range and subgroup properties of FeLV-C retained certain FeLV-A-like properties in that they were non-cytopathogenic in 3201B feline T cells and readily induced viraemia in weanling animals. They also induced a profound anaemia in neonates which had a more prolonged course than that induced by FeLV-C/Sarma and which was macrocytic rather than non-regenerative in nature. Although receptor specificity and a major determinant of pathogenicity segregate with Vr1, it appears that sequences elsewhere in the genome influence infectivity and pathogenicity independently of the subgroup phenotype.