HERV-K(HML-2),人类内源性逆转录病毒(HERV)的最年轻的进化枝,包括许多完整的或几乎完整的提供物,但在人类中尚未发现有复制能力的HML-2病毒。HML-2相关的外在其他灵长类动物中存在,包括恒河猴,但猕猴中HML-2活性的程度和时间仍不清楚.我们已经在恒河猴中鉴定出145个类似HML-2的原病毒,包括一群年轻人,恒河猴特异性插入。年龄估计,完整的ORF,这些插入的插入多态性与猕猴最近或正在进行的感染活动一致。106个条件形成一个进化枝,其特征在于env和3'LTR之间的~750bp序列,源自与HERV-K(HML-8)相关病毒的古老重组。这个进化枝在旧世界的猴子(OWM)中发现,但不是大猿,表明它起源于猿/OWM分裂之后。我们在白颊长臂猿中发现了类似的条件;长臂猿插入簇在OWM重组进化枝中,表明从OWM到长臂猿的种间传播。最年轻的原的LTR在U3中缺失,破坏了Rec响应元件(RcRE),未剪接的病毒RNA的核输出所需的。我们表明,HML-8衍生区域作为Rec独立的组成型运输元件(CTE),表明祖先的Rec-RcRE输出系统被CTE机制取代。
HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact
proviruses, but no replication competent HML-2
proviruses have been identified in humans. HML-2-related
proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact open reading frames, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 106 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3\' long terminal repeat (LTR), derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar
proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest
proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8-derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec-RcRE export system was replaced by a CTE mechanism.
Just as we study fossils to understand how animals and plants have evolved, we can study ancient viruses to understand how diseases have emerged and changed over long periods. Unlike fossils, viruses do not leave visible traces in the ground but, instead, they leave viral genes known as endogenous viral elements (or EVEs) that become permanently incorporated in their host’s DNA. HML-2s are the youngest known EVEs in the human genome. They have evolved gradually by accumulating lots of small genetic changes and no longer actively infect humans. But these virus remnants have long been suspected to play a role in prostate cancer, lupus and other human diseases. Rhesus macaques and other monkeys also have HML-2s but these are less well studied than human HML-2s. Monkeys are often used as models of human biology in research studies, therefore, understanding how HML-2s have evolved in rhesus macaques may enable researchers to establish this monkey as a model for investigating the role of HML-2s in humans. To investigate this possibility, Williams et al. searched for HML-like EVEs in rhesus macaque genomes published in previous studies. The experiments found that, unlike human HML-2s, the macaque HML-2s underwent a sudden genetic transformation millions of years ago. They acquired a new gene from another virus that completely changed how the macaque HML-2s leave a compartment within the cells of their host that contains most of the host’s genome – a key step in the life cycle of viruses. The data also suggest that HML-2s may still be actively infecting macaques today and that these EVEs jumped from monkeys into gibbons. This is the first known example of HML-2s moving between different types of primates and it indicates there may be a risk that macaque HML-2s could infect humans. In the future, the findings of Williams et al. may help researchers develop new approaches to treat prostate cancer and other diseases linked with HML-2s in humans.