title: High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences.
abstract: BACKGROUND
  HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5α (hTRIM5α) could contribute to these differences.
  
  
  RESULTS
  We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5α was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5α to that measured in cells in which hTRIM5α activity was inhibited by overexpression of hTRIM5γ.The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5α expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratory-adapted HIV-2 clones. High hTRIM5α susceptibility was found in all HIV-2 subtypes. In this series of viruses, susceptibility to hTRIM5α was not significantly affected by the presence of a proline at position 119 or by the number of prolines at positions 119, 159 or 178 in HIV-2 CA. No significant correlation was found between HIV-2 viremia and sensitivity to hTRIM5α.
  
  
  CONCLUSIONS
  HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5α. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans.
authors: INSERM U941, Paris 75010, France.
authors: Junko S
authors: JS
authors: Takeuchi
authors: Benjamin
authors: B
authors: Perche
authors: Julie
authors: J
authors: Migraine
authors: Séverine
authors: S
authors: Mercier-Delarue
authors: Diane
authors: D
authors: Ponscarme
authors: François
authors: F
authors: Simon
authors: François
authors: F
authors: Clavel
authors: Béatrice
authors: B
authors: Labrosse
mesh_terms: D000090103:Antiviral Restriction Factors; D036022:Capsid Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D055550:Protein Stability; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D036022:Capsid Proteins; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
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