Department of Infectious Diseases, Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany.
Laboratory of Regulation of Intracellular Proteolysis, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Int J Mol Sci. 2021 Nov 17;22(22):12398. doi: 10.3390/ijms222212398.
About 8% of our genome is composed of sequences from Human Endogenous Retroviruses (HERVs). The HERV-K (HML.2) family, here abbreviated HML.2, is able to produce virus particles that were detected in cell lines, malignant tumors and in autoimmune diseases. Parameters and properties of HML.2 released from teratocarcinoma cell lines GH and Tera-1 were investigated in detail. In most experiments, analyzed viruses were purified by density gradient centrifugation. HML.2 structural proteins, reverse transcriptase (RT) activity, viral RNA (vRNA) and particle morphology were analyzed. The HML.2 markers were predominantly detected in fractions with a buoyant density of 1.16 g/cm. Deglycosylation of TM revealed truncated forms of transmembrane (TM) protein. Free virions and extracellular vesicles (presumably microvesicles-MVs) with HML.2 elements, including budding intermediates, were detected by electron microscopy. Viral elements and assembled virions captured and exported by MVs can boost specific immune responses and trigger immunomodulation in recipient cells. Sequencing of cDNA clones demonstrated exclusive presence of HERV-K108 in HML.2 from Tera-1 cells. Not counting two recombinant variants, four known sequences were found in HML.2 from GH cells. Obtained results shed light on parameters and morphology of HML.2. A possible mechanism of HML.2-induced diseases is discussed.
我们的基因组大约有 8%是由人类内源性逆转录病毒（HERV）的序列组成。HERV-K（HML.2）家族，在这里缩写为 HML.2，能够产生病毒颗粒，这些病毒颗粒已在细胞系、恶性肿瘤和自身免疫性疾病中被检测到。我们详细研究了源自畸胎瘤细胞系 GH 和 Tera-1 的 HML.2 释放的参数和特性。在大多数实验中，分析的病毒通过密度梯度离心进行纯化。分析了 HML.2 结构蛋白、逆转录酶（RT）活性、病毒 RNA（vRNA）和颗粒形态。HML.2 标志物主要在浮力密度为 1.16 g/cm 的级分中检测到。TM 的去糖基化揭示了跨膜（TM）蛋白的截断形式。通过电子显微镜检测到带有 HML.2 元件的游离病毒和细胞外囊泡（推测为微泡-MVs），包括出芽中间体。病毒元件和组装的病毒粒子被 MVs 捕获和输出，可以增强特异性免疫反应，并在受体细胞中引发免疫调节。cDNA 克隆的测序表明，Tera-1 细胞中的 HML.2 仅存在 HERV-K108。在 GH 细胞中的 HML.2 中发现了四个已知序列，不包括两个重组变体。获得的结果阐明了 HML.2 的参数和形态。讨论了 HML.2 诱导疾病的可能机制。
