Rohn J L, Moser M S, Gwynn S R, Baldwin D N, Overbaugh J
Department of Microbiology, University of Washington, Seattle 98195, USA.
J Virol. 1998 Apr;72(4):2686-96. doi: 10.1128/JVI.72.4.2686-2696.1998.
Studies of feline leukemia virus (FeLV) have illustrated the importance of the genotype of the infecting virus in determining disease outcome. In FeLV infections, as in other retroviral infections, it is less clear how virus variants that evolve from the transmitted virus affect pathogenesis. We previously reported an analysis of the genotypic changes that occur in the viral envelope gene (env) in cats infected with a prototype transmissible FeLV clone, 61E (J. Rohn, M. Linenberger, E. Hoover, and J. Overbaugh, J. Virol. 68:2458-2467, 1994). In one cat, each variant (81T) had evolved, in addition to scattered amino acid changes, a four-amino-acid insertion with respect to 61E. This insertion was located at the same site in the extracellular envelope glycoprotein where the immunodeficiency-inducing molecular clone 61C possesses a six-amino-acid insertion critical for its pathogenic phenotype, although the sequences of the insertions were distinct. To determine whether acquisition of the four-amino-acid insertion was associated with a change in the replication or cytopathic properties of the virus, we constructed chimeras encoding 81T env genes in a 61E background. One representative chimeric virus, EET(TE)-109, was highly cytopathic despite the fact that it replicated with delayed kinetics in the feline T-cell line 3201 compared to the parental 61E virus. The phenotype of this virus was also novel compared to other FeLVs, including both the parental virus 61E and the immunodeficiency-inducing variant 61C, because infection of T cells was associated with syncytium formation. Moreover, in single-cycle infection assays, the 81T-109 envelope demonstrated receptor usage properties distinct from those of both 61E and 61C envelope. Thus, these studies demonstrate the evolution of a novel T-cell cytopathic and syncytium-inducing FeLV in the host. The 81T virus will be valuable for dissecting the mechanism of T-cell killing by cytopathic variants in the FeLV model.
猫白血病病毒（FeLV）的研究表明，感染病毒的基因型在决定疾病转归方面具有重要意义。在FeLV感染中，与其他逆转录病毒感染一样，从传播的病毒进化而来的病毒变体如何影响发病机制尚不清楚。我们之前报道了对感染原型可传播FeLV克隆61E的猫的病毒包膜基因（env）中发生的基因型变化的分析（J. Rohn、M. Linenberger、E. Hoover和J. Overbaugh，《病毒学杂志》68:2458 - 2467，1994年）。在一只猫中，每个变体（81T）除了有零散的氨基酸变化外，相对于61E还进化出了一个四氨基酸插入。该插入位于细胞外包膜糖蛋白的同一位置，免疫缺陷诱导分子克隆61C在该位置具有对其致病表型至关重要的六氨基酸插入，尽管插入序列不同。为了确定获得四氨基酸插入是否与病毒复制或细胞病变特性的变化相关，我们构建了在61E背景下编码81T env基因的嵌合体。一种代表性的嵌合病毒EET(TE)-109具有高度细胞病变性，尽管与亲代61E病毒相比，它在猫T细胞系3201中复制动力学延迟。与其他FeLV相比，包括亲代病毒61E和免疫缺陷诱导变体61C，这种病毒的表型也很新颖，因为T细胞感染与合胞体形成有关。此外，在单循环感染试验中，81T - 109包膜表现出与61E和61C包膜不同的受体使用特性。因此，这些研究证明了宿主中一种新型的T细胞细胞病变性和合胞体诱导性FeLV的进化。81T病毒对于剖析FeLV模型中细胞病变变体杀伤T细胞的机制将具有重要价值。
