Gudmundsson Bjarki, Jónsson Stefán Ragnar, Olafsson Oddur, Agnarsdóttir Gudrún, Matthíasdóttir Sigrídur, Georgsson Gudmundur, Torsteinsdóttir Sigurbjorg, Svansson Vilhjálmur, Kristbjornsdóttir Helga Bryndís, Franzdóttir Sigrídur Rut, Andrésson Olafur S, Andrésdóttir Valgerdur
Institute for Experimental Pathology, University of Iceland, Keldur v/Vesturlandsveg, 112 Reykjavík, Iceland.
J Virol. 2005 Dec;79(24):15038-42. doi: 10.1128/JVI.79.24.15038-15042.2005.
Maedi-visna virus (MVV) is a lentivirus of sheep sharing several key features with the primate lentiviruses. The virus causes slowly progressive diseases, mainly in the lungs and the central nervous system of sheep. Here, we investigate the molecular basis for the differential growth phenotypes of two MVV isolates. One of the isolates, KV1772, replicates well in a number of cell lines and is highly pathogenic in sheep. The second isolate, KS1, no longer grows on macrophages or causes disease. The two virus isolates differ by 129 nucleotide substitutions and two deletions of 3 and 15 nucleotides in the env gene. To determine the molecular nature of the lesions responsible for the restrictive growth phenotype, chimeric viruses were constructed and used to map the phenotype. An L120R mutation in the CA domain, together with a P205S mutation in Vif (but neither alone), could fully convert KV1772 to the restrictive growth phenotype. These results suggest a functional interaction between CA and Vif in MVV replication, a property that may relate to the innate antiretroviral defense mechanisms in sheep.
梅迪 - 维斯纳病毒（MVV）是一种绵羊慢病毒，与灵长类慢病毒具有几个关键特征。该病毒会引发缓慢进展的疾病，主要影响绵羊的肺部和中枢神经系统。在此，我们研究两种MVV分离株生长表型差异的分子基础。其中一个分离株KV1772在多种细胞系中复制良好，且对绵羊具有高度致病性。第二个分离株KS1不再能在巨噬细胞上生长，也不会引发疾病。这两种病毒分离株在env基因上有129个核苷酸替换以及两个分别缺失3个和15个核苷酸的情况。为了确定导致限制性生长表型的损伤的分子性质，构建了嵌合病毒并用于定位该表型。CA结构域中的L120R突变，以及Vif中的P205S突变（但单独一个都不行），可将KV1772完全转变为限制性生长表型。这些结果表明在MVV复制过程中CA和Vif之间存在功能相互作用，这一特性可能与绵羊的固有抗逆转录病毒防御机制有关。
