Structural and Functional Analysis of Prehistoric Lentiviruses Uncovers an Ancient Molecular Interface

DOI: 10.1016/j.chom.2010.08.006
PMID: 20833376

Authors: David C. Goldstone (MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK) , Melvyn W. Yap (MRC National Institute for Medical Research) , Laura E. Robertson (MRC National Institute for Medical Research) , Lesley F. Haire (MRC National Institute for Medical Research) , William R. Taylor (MRC National Institute for Medical Research) , Aris Katzourakis (University of Oxford) , Jonathan P. Stoye (MRC National Institute for Medical Research) , Ian A. Taylor (MRC National Institute for Medical Research)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Host & Microbe , VOL 8 (3) , PAGES 248 - 259

State: Published (Approved)
Published: September 2010
Diamond Proposal Number(s): 1228

Abstract: 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.

Journal Keywords: Base; Capsid; Capsid; Crystallography; X-Ray; Cyclophilin; DNA; Endogenous; Evolution; Molecular; Gene; gag; Genes; Viral; Genes; gag; Lemur; Lentivirus; Lentiviruses; Primate; Models; Molecular; Protein; Tertiary; Rabbits; Recombinant; Virion

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

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