Background Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data. Results All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression. Conclusions Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells.

中文翻译：

---

考拉逆转录病毒的多样性、传播性和疾病关联

背景 考拉感染了以外源或内源病毒形式存在的考拉逆转录病毒 (KoRV)。KoRV 具有遗传多样性，可能与多达 10 种包膜亚型 (AJ) 共同感染；KoRV-A 是原型内源形式。KoRV-B 首先在美国一家动物园的少数白血病患病率增加的考拉中发现，并与其他癌症和衣原体疾病增加有关。为了更好地了解 KoRV 变异的分子流行病学以及病毒载量 (VL) 增加对传播性和致病性的影响，我们开发了亚型特异性定量 PCR (qPCR) 检测方法并测试了美国动物园考拉的血液和组织样本（n = 78） , 两个澳大利亚动物园 (n = 27) 和澳大利亚野生动物 (n = 21)。我们使用可用的临床、人口统计和谱系数据分析了 PCR 结果。结果所有考拉都感染了 KoRV-A。美国一家动物园的少数考拉 (10.3%) 也感染了非 A 亚型，而在澳大利亚动物园的考拉中发现了更高的非 A 亚型患病率 (59.3%)。来自一处的野生考拉只感染了 KoRV-A。我们在死于白血病/淋巴瘤和其他肿瘤的考拉中观察到感染和非 A 亚型血浆 VL 的显着关联，并报告了 KoRV-A 阳性动物的癌症诊断。非 A 亚型的感染和 VL 与年龄或性别无关。非 A 亚型的传播发生在大坝到后代，并且很可能发生在成人与成人的接触之后，但未评估与接触类型的关联。对感染了高血浆 KoRV-A、-B、-F 不影响 VL 或疾病进展。结论 我们的结果显示非 A KoRV 感染和血浆 VLs 与白血病和其他癌症之间存在显着关联。尽管我们确认了这些变体的大坝到后代的传播，但我们也表明其他途径也是可能的。我们经过验证的 qPCR 检测将有助于进一步了解 KoRV 流行病学及其对暴露于考拉的人类的人畜共患病传播潜力，因为 KoRV 可以感染人类细胞。