Structural and functional analysis of prehistoric lentiviruses uncovers an ancient molecular interface

Cell Host Microbe. 2010 Sep 16;8(3):248-59. doi: 10.1016/j.chom.2010.08.006.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Capsid / metabolism
  • Capsid Proteins / chemistry*
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Crystallography, X-Ray
  • Cyclophilin A / chemistry
  • Cyclophilin A / metabolism*
  • DNA Methylation
  • Endogenous Retroviruses / chemistry*
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / physiology
  • Evolution, Molecular*
  • Gene Products, gag / chemistry
  • Gene Products, gag / metabolism
  • Genes, Viral
  • Genes, gag
  • Lemur / virology
  • Lentivirus / chemistry*
  • Lentivirus / genetics*
  • Lentivirus / physiology
  • Lentiviruses, Primate / chemistry
  • Lentiviruses, Primate / genetics
  • Lentiviruses, Primate / physiology
  • Models, Molecular
  • Protein Structure, Tertiary
  • Rabbits
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Virion / metabolism

Substances

  • Capsid Proteins
  • Gene Products, gag
  • Recombinant Fusion Proteins
  • Cyclophilin A

Associated data

  • PDB/2XGU
  • PDB/2XGV
  • PDB/2XGY