Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Cell Host Microbe. 2010 Sep 16;8(3):248-59. doi: 10.1016/j.chom.2010.08.006.
Lentiviruses are widespread in a variety of vertebrates, often associated with chronic disease states. However, until the recent discovery of the prehistoric endogenous lentiviruses in rabbits (RELIK) and lemurs (PSIV), it was thought that lentiviruses had no capacity for germline integration and were only spread horizontally in an exogenous fashion. The existence of RELIK and PSIV refuted these ideas, revealing lentiviruses to be present in a range of mammals, capable of germline integration, and far more ancient than previously thought. Using Gag sequences reconstructed from the remnants of these prehistoric lentiviruses, we have produced chimeric lentiviruses capable of infecting nondividing cells and determined structures of capsid domains from PSIV and RELIK. We show that the structures from these diverse viruses are highly similar, containing features found in modern-day lentiviruses, including a functional cyclophilin-binding loop. Together, these data provide evidence for an ancient capsid-cyclophilin interaction preserved throughout lentiviral evolution.
慢病毒广泛存在于各种脊椎动物中，通常与慢性疾病状态有关。然而，直到最近在兔子（RELIK）和狐猴（PSIV）中发现史前内源性慢病毒（prehistoric endogenous lentiviruses）之前，人们一直认为慢病毒没有种系整合的能力，只能以外源的方式水平传播。RELIK 和 PSIV 的存在驳斥了这些观点，表明慢病毒存在于一系列哺乳动物中，能够进行种系整合，而且比之前认为的要古老得多。我们使用从这些史前慢病毒的残余物重建的 gag 序列，产生了能够感染非分裂细胞的嵌合慢病毒，并确定了 PSIV 和 RELIK 的衣壳结构域的结构。我们表明，来自这些不同病毒的结构非常相似，包含了在现代慢病毒中发现的特征，包括一个功能性亲环素结合环。这些数据共同为整个慢病毒进化过程中保守的古老衣壳-亲环素相互作用提供了证据。
