title: The human TRIM5alpha restriction factor mediates accelerated uncoating of the N-tropic murine leukemia virus capsid.
abstract: The host cell factors TRIM5alpha(hu) and Fv-1 restrict N-tropic murine leukemia virus (N-MLV) infection at an early postentry step before or after reverse transcription, respectively. Interestingly, the identity of residue 110 of the MLV capsid determines susceptibility to both TRIM5alpha(hu) and Fv-1. In this study, we investigate the fate of the MLV capsid in cells expressing either the TRIM5alpha(hu) or Fv-1 restriction factor. The expression of TRIM5alpha(hu), but not Fv-1, specifically promoted the premature conversion of particulate N-MLV capsids within infected cells to soluble capsid proteins. The TRIM5alpha(hu)-mediated disassembly of particulate N-MLV capsids was dependent upon residue 110 of the viral capsid. Furthermore, the deletion or disruption of TRIM5alpha(hu) domains necessary for potent N-MLV restriction completely abrogated the disappearance of particulate N-MLV capsids observed with wild-type TRIM5alpha(hu). These results suggest that premature disassembly of the viral capsid contributes to the restriction of N-MLV infection by TRIM5alpha(hu), but not by Fv-1.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Perron
authors.forename: Matthew
authors.initials: M
authors.lastname: Stremlau
authors.forename: Mark
authors.initials: M
authors.lastname: Lee
authors.forename: Hassan
authors.initials: H
authors.lastname: Javanbakht
authors.forename: Byeongwoon
authors.initials: B
authors.lastname: Song
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000090103:Antiviral Restriction Factors; D001483:Base Sequence; D002213:Capsid / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D017931:DNA Primers; C103189:Fv1 protein, mouse; D011506:Proteins; D011993:Recombinant Fusion Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases