Transboundary Animal Diseases Centre, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
J Virol. 2020 May 18;94(11). doi: 10.1128/JVI.00019-20.
Koala retrovirus (KoRV) is of an interest to virologists due to its currently active endogenization into the koala () genome. Although KoRV has frequently been isolated in wild and captive koala populations, its pathogenesis and transmission remain to be fully characterized, and most previous research has concentrated on adult koalas rather than on joeys. Here, we characterized KoRV isolates obtained from a deceased male joey and its parents (animals reared in a Japanese zoo) to investigate KoRV transmission mode and pathogenesis. We sequenced the KoRV long terminal repeat (LTR) and envelope genes isolated from the joey and its parents and found KoRV-A and KoRV-C in genomic DNA from both the parents and the joey. Notably, both parents were also positive for KoRV-B, whereas the joey was KoRV-B negative, further confirming that KoRV-B is an exogenous strain. The KoRV LTR sequence of the joey was considerably closer to that of its sire than its dam. For further characterization, total KoRV, KoRV-A, KoRV-B, and KoRV-C proviral loads were quantified in peripheral blood mononuclear cells from the parents and in blood samples from the joey. Total KoRV, KoRV-A, and KoRV-C proviral loads were also quantified for different tissues (bone, liver, kidney, lung, spleen, heart, and muscle) from the joey, revealing differences suggestive of a distinct tissue tropism (highest total KoRV proviral load in the spleen and lowest in bone). The amount of KoRV-C in the parents was less than that in the joey. Our findings contribute to an improved understanding of KoRV pathogenesis and transmission mode and highlight useful areas for future research. KoRV is unique among retroviruses in that one strain (KoRV-A) is undergoing endogenization, whereas the other main subtype (KoRV-B) and another subtype (KoRV-C) are reportedly exogenous strains. Its transmission and pathogenesis are of interest in the study of retroviruses and are crucial for any conservation strategy geared toward koala health. This study provides new evidence on the modes of KoRV transmission from parent koalas to their joey. We found vertical transmission of KoRV-A, confirming its endogenization, but with closer conservation between the joey and its sire than its dam (previous reports on joeys are rare but have postulated dam-to-joey vertical transmission). This is also the first report of a KoRV-B-negative joey from KoRV-B-positive parents, contrasting with the few previous reports of 100% transmission of KoRV-B from dams to joeys. Thus, the results in this study give some novel insights for the transmission mode of KoRV.
考拉逆转录病毒（KoRV）因其目前在考拉基因组中活跃的内源性而引起病毒学家的关注。尽管 KoRV 经常在野生和圈养的考拉群体中分离出来，但它的发病机制和传播仍未完全阐明，而且大多数先前的研究都集中在成年考拉身上，而不是幼考拉身上。在这里，我们对一只死亡的雄性幼考拉及其父母（在日本动物园饲养的动物）中分离出的 KoRV 分离株进行了特征描述，以研究 KoRV 的传播模式和发病机制。我们对从幼考拉及其父母中分离出的 KoRV 长末端重复（LTR）和包膜基因进行了测序，发现来自父母和幼考拉的基因组 DNA 中均存在 KoRV-A 和 KoRV-C。值得注意的是，父母双方均为 KoRV-B 阳性，而幼考拉为 KoRV-B 阴性，进一步证实 KoRV-B 是一种外源性株。幼考拉的 KoRV LTR 序列与其父本比其母本更接近。为了进一步进行特征描述，我们定量检测了父母外周血单核细胞和幼考拉血液样本中的总 KoRV、KoRV-A、KoRV-B 和 KoRV-C 前病毒载量。还定量检测了幼考拉不同组织（骨、肝、肾、肺、脾、心和肌肉）中的总 KoRV、KoRV-A 和 KoRV-C 前病毒载量，结果显示出不同的组织嗜性差异（脾脏中的总 KoRV 前病毒载量最高，骨骼中的最低）。父母的 KoRV-C 量少于幼考拉。我们的研究结果有助于更好地了解 KoRV 的发病机制和传播模式，并突出了未来研究的有用领域。KoRV 是逆转录病毒中独一无二的，一种株（KoRV-A）正在进行内源性，而另一种主要亚型（KoRV-B）和另一种亚型（KoRV-C）据报道是外源性株。它的传播和发病机制是逆转录病毒研究的热点，对于任何以考拉健康为目标的保护策略都至关重要。本研究提供了有关亲代考拉向幼考拉传播 KoRV 的方式的新证据。我们发现 KoRV-A 的垂直传播，证实了其内源性，但幼考拉与其父本的保守性比其母本更高（先前关于幼考拉的报道很少，但推测存在母考拉到幼考拉的垂直传播）。这也是首次从 KoRV-B 阳性父母中分离出 KoRV-B 阴性幼考拉的报道，与先前关于 KoRV-B 从母考拉到幼考拉 100%传播的少数报道形成对比。因此，本研究的结果为 KoRV 的传播模式提供了一些新的见解。
