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Homology-based identification of capsid determinants that protect HIV1 from human TRIM5α restriction.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Maillard Pierre V, Zoete Vincent, Michielin Olivier, Trono Didier,
Project KRAB/KAP1 epigenetic regulation in the control of memory and emotional traits: from mice to humans.
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Original article (peer-reviewed)

Journal The Journal of biological chemistry
Volume (Issue) 286(10)
Page(s) 8128 - 40
Title of proceedings The Journal of biological chemistry
DOI 10.1074/jbc.M110.187609

Abstract

The tropism of retroviruses relies on their ability to exploit cellular factors for their replication as well as to avoid host-encoded inhibitory activities such as TRIM5α. N-tropic murine leukemia virus is sensitive to human TRIM5α (huTRIM5α) restriction, whereas human immunodeficiency virus type 1 (HIV1) escapes this antiviral factor. We previously revealed that mutation of four critical amino acid residues within the capsid can render murine leukemia virus resistant to huTRIM5α. Here, we exploit the high degree of conservation in the tertiary structure of retroviral capsids to map the corresponding positions on the HIV1 capsid. We then demonstrated that, when changes were introduced at some of these positions, HIV1 becomes sensitive to huTRIM5α restriction, a phenomenon reinforced by additionally mutating the nearby cyclophilin A binding loop of the viral protein. These results indicate that retroviruses have evolved similar mechanisms to escape TRIM5α restriction via the interference of structurally homologous determinants in the viral capsid.
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