牛伏脉病毒（BFVbta）展现了极高程度的细胞关联复制，这在已知其他伏脉病毒中都是前所未有的。有趣的是，最近的研究表明，BFVbta能够在体外适应高滴度（HT）细胞无传播，这是由于在不断的BFVbta无细胞传播及其在不朽化的MDBK牛细胞中重复往复过程中所获得的遗传变化。从高滴度BFVbta Riems细胞无变异体（HT BFVbta Riems）获得的分子克隆体在MDBK细胞培养中得到详细表征。然而，近年来，越来越清楚的是，用于病毒生长和病毒复制与病毒-细胞相互作用功能研究的宿主细胞的来源起着重要作用。已建立的细胞系，大多源自肿瘤细胞，但有时也进行实验性不朽化和转化，常常显示出异常特征，例如生长、代谢和遗传方面的异常。即使是最先进的原代细胞类器官培养也不能复制真实宿主的条件，特别是涉及细胞多样性以及先天和适应性免疫的作用的条件。因此，为了确定克隆 wt 和 HT BFVbta Riems 变体的整体复制特性，我们进行了一项小规模动物试验。原始的 BFVbta Riems 株系和其 HT 变体 BFVbta Riems 的复制情况得到了分析。两种 BFVbta 变体都在小牛中建立了感染，外周血单个核细胞中存在原些病毒，并诱导产生Gag特异性抗体。此外，在BFV感染小牛的周围血液白细胞中检测到了相关的宿主固有免疫反应模式。令人惊讶的是，犊牛注入后两周的Gag序列分析结果显示，HT BFVbta变体呈高度的基因还原状态，恢复到野生型（父本BFVbta基因型）。

Bovine foamy virus (BFVbta) displays a very high degree of cell-associated replication which is unprecedented even among the other known foamy viruses. Interestingly, recent studies have shown that it can in fact adapt in vitro to high-titer (HT) cell-free transmission due to genetic changes acquired during repeated rounds of cell-free BFVbta passages in immortalized bovine MDBK cells. Molecular clones obtained from the HT BFVbta Riems cell-free variant (HT BFVbta Riems) have been thoroughly characterized in MDBK cell cultures However, during recent years, it has become increasingly clear that the source of the host cells used for virus growth and functional studies of virus replication and virus-cell interactions plays a paramount role. Established cell lines, mostly derived from tumors, but occasionally experimentally immortalized and transformed, frequently display aberrant features relating, for example. to growth, metabolism, and genetics. Even state-of-the-art organoid cultures of primary cells cannot replicate the conditions in an authentic host, especially those concerning cell diversity and the role of innate and adaptive immunity. Therefore, to determine the overall replication characteristics of the cloned wt and HT BFVbta Riems variant, we conducted a small-scale animal pilot study. The replication of the original wt BFVbta Riems isolate, as well as that of its HT variant, were analyzed. Both BFVbta variants established infection in calves, with proviruses in peripheral blood mononuclear cells and induced Gag-specific antibodies. In addition, a related pattern in the host innate immune reaction was detected in the peripheral blood leukocytes of the BFV-infected calves. Surprisingly, an analysis of the Gag sequence two weeks post-inoculation revealed that the HT BFVbta variant showed a very high level of genetic reversion to the wild type (parental BFVbta genotype).