PLoS Pathogens (Jan 2012)

CPSF6 defines a conserved capsid interface that modulates HIV-1 replication.

  • Amanda J Price,
  • Adam J Fletcher,
  • Torsten Schaller,
  • Tom Elliott,
  • KyeongEun Lee,
  • Vineet N KewalRamani,
  • Jason W Chin,
  • Greg J Towers,
  • Leo C James

DOI
https://doi.org/10.1371/journal.ppat.1002896
Journal volume & issue
Vol. 8, no. 8
p. e1002896

Abstract

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The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.