Clinical Laboratory and Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Virus Res. 2015 Feb 2;197:137-50. doi: 10.1016/j.virusres.2014.12.025. Epub 2014 Dec 30.
It is a remarkable feature for a retrovirus that an infection with feline leukemia virus (FeLV) can result in various outcomes. Whereas some cats contain the infection and show a regressive course, others stay viremic and succumb to the infection within a few years. We hypothesized, that differences in the infection outcome might be causally linked to the viral RNA and provirus loads within the host and these loads therefore may give additional insight into the pathogenesis of the virus. Thus, the goals of the present study were to follow-up on experimentally infected cats and investigate tissues from cats with different infection outcomes using sensitive, specific TaqMan real-time PCR and reverse transcriptase (RT)-PCR. Nineteen experimentally FeLV-A/Glasgow-1-infected cats were categorized into having regressive, progressive or reactivated FeLV infection according to follow-up of FeLV p27 antigen detection in the blood. Remarkably, regressively infected cats showed detectable provirus and viral RNA loads in almost all of the 27 tested tissues, even many years after virus exposure. Moreover, some regressively infected cats reactivated the infection, and these cats had intermediate to high viral RNA and provirus tissue loads. The highest loads were found in viremic cats, independent of their health status. Tissues that represented sites of virus replication and shedding revealed the highest viral RNA and provirus loads, while the lowest loads were present in muscle and nerve tissues. A supplementary analysis of 20 experimentally infected cats with progressive infection revealed a median survival time of 3.1 years (range from 0.6 to 6.5 years); ∼70% (n=14) of these cats developed lymphoma, while leukemia and non-regenerative anemia were observed less frequently. Our results demonstrate that the different infection outcomes are associated with differences in viral RNA and provirus tissue loads. Remarkably, no complete clearance of FeLV viral RNA or provirus was detected in cats with regressive infection, even up to 12 years after exposure. In several cases FeLV reactivation could be observed. Thus, retroviruses integrated as provirus into the host's genome, could not be eliminated completely by the host and maintained their full potential for replication and reactivation.
逆转录病毒的一个显著特征是，猫白血病病毒（FeLV）感染可导致多种结果。有些猫携带感染并呈现退行性病程，而另一些猫则持续病毒血症，并在数年内死于感染。我们假设，感染结果的差异可能与宿主中的病毒 RNA 和前病毒载量有关，因此这些载量可能为病毒的发病机制提供更多的见解。因此，本研究的目的是对实验感染的猫进行随访，并使用敏感、特异的 TaqMan 实时 PCR 和逆转录酶（RT）-PCR 检测具有不同感染结果的猫的组织。19 只实验性感染 FeLV-A/Glasgow-1 的猫根据血液中 FeLV p27 抗原检测的随访结果，分为退行性、进行性或再激活 FeLV 感染。值得注意的是，退行性感染的猫在几乎所有 27 个检测的组织中都检测到可检测的前病毒和病毒 RNA 载量，即使在病毒暴露多年后也是如此。此外，一些退行性感染的猫重新激活了感染，这些猫的病毒 RNA 和前病毒组织载量处于中等至高水平。最高的载量出现在病毒血症的猫中，而与它们的健康状况无关。代表病毒复制和脱落部位的组织显示出最高的病毒 RNA 和前病毒载量，而肌肉和神经组织的载量最低。对 20 只进行性感染的实验感染猫进行的补充分析显示，中位存活时间为 3.1 年（范围从 0.6 到 6.5 年）；这些猫中约 70%（n=14）发展为淋巴瘤，而白血病和非再生性贫血则较少见。我们的结果表明，不同的感染结果与病毒 RNA 和前病毒组织载量的差异有关。值得注意的是，在退行性感染的猫中，即使在暴露后长达 12 年，也没有检测到 FeLV 病毒 RNA 或前病毒的完全清除。在一些情况下可以观察到 FeLV 的重新激活。因此，整合到宿主基因组中的逆转录病毒作为前病毒，不能被宿主完全清除，并保持其复制和重新激活的全部潜力。
