Nishikaku Kohei, Yonezawa Takahiro, Nishibori Masahide, Harada Masashi, Kawaguchi Fuki, Sasazaki Shinji, Torii Yasushi, Imakawa Kazuhiko, Kawai Kuniko, Liu Jianquan, Mannen Hideyuki, Kobayashi Tomoko
Laboratory of Animal Health, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Atsugi, Japan.
Laboratory of Animal Genetics, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Atsugi, Japan.
Front Microbiol. 2022 Jun 24;13:917324. doi: 10.3389/fmicb.2022.917324. eCollection 2022.
Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis, is currently one of the most important pathogens affecting the cattle industry worldwide. Determining where and in which host it originated, and how it dispersed across continents will provide valuable insights into its historical emergence as the cattle pathogen. Various species in the genus were domesticated in Asia, where they also diversified. As native cattle (taurine cattle, zebu cattle, yak, and water buffalo) are indigenous and adapted to local environments, we hypothesized that Asian native cattle could have harbored BLV and, therefore, that they were important for virus emergence, maintenance, and spread. In this study, phylogeographic and ancestral trait analyses-including sequences obtained from Asian native cattle-were used to reconstruct the evolutionary history of BLV. It was shown that, since its probable emergence in Asia, the virus spread to South America and Europe via international trade of live cattle. It was inferred that zebu cattle were the hosts for the early origin of BLV, while taurine cattle played the significant role in the transmission worldwide. In addition, the results of positive selection analysis indicate that yak had a substantially minor role in the transmission of this virus. In this study, endogenous deltaretrovirus sequences in bats, collected in Asian countries, were also analyzed on whether these sequences were present in the bat genome. Endogenous deltaretrovirus sequences were detected from bat species endemic to specific regions and geographically isolated for a long time. Endogenous deltaretrovirus sequences from these geographically isolated species represent ancient exogenous deltaretroviruses distributions. The phylogenetic analysis revealed that these newly obtained endogenous deltaretrovirus sequences were closely related to those of BLV from Asian native cattle, indicating that BLV-related ancient deltaretroviruses circulated in Asia long before the emergence of BLV. Together, our analyses provide evidence for origin and spatiotemporal dynamics of BLV.
牛白血病病毒（BLV）是地方流行性牛白血病的病原体，目前是影响全球养牛业的最重要病原体之一。确定它的起源地、宿主以及如何跨洲传播，将为其作为牛病原体的历史出现提供有价值的见解。该属的各种物种在亚洲被驯化，在那里它们也发生了多样化。由于本地牛（黄牛、瘤牛、牦牛和水牛）是本土的且适应当地环境，我们推测亚洲本地牛可能携带了BLV，因此它们对病毒的出现、维持和传播很重要。在这项研究中，系统发育地理学和祖先性状分析（包括从亚洲本地牛获得的序列）被用于重建BLV的进化历史。结果表明，自其可能在亚洲出现以来，该病毒通过活牛国际贸易传播到了南美洲和欧洲。据推断，瘤牛是BLV早期起源的宿主，而黄牛在全球传播中起了重要作用。此外，正选择分析结果表明牦牛在该病毒传播中的作用极小。在这项研究中，还分析了在亚洲国家收集的蝙蝠体内的内源性δ逆转录病毒序列，以确定这些序列是否存在于蝙蝠基因组中。从特定地区特有的、长期地理隔离的蝙蝠物种中检测到了内源性δ逆转录病毒序列。这些地理隔离物种的内源性δ逆转录病毒序列代表了古代外源性δ逆转录病毒的分布。系统发育分析表明，这些新获得的内源性δ逆转录病毒序列与亚洲本地牛的BLV序列密切相关，这表明与BLV相关的古代δ逆转录病毒在BLV出现之前很久就在亚洲传播。总之，我们的分析为BLV的起源和时空动态提供了证据。
