Trim5alpha accelerates degradation of cytosolic capsid associated with productive HIV-1 entry.
The TRIM5alpha (tripartite motif 5alpha protein) has been linked to the cross-species restriction in human immunodeficiency virus type 1 (HIV-1) infection of non-human cells, but the mechanism by which this occurs remains to be fully elucidated. Here we demonstrate that the capsid (CA) protein of HIV-1 is more rapidly degraded in cells expressing monkey TRIM5alpha than in cells expressing human TRIM5alpha. Other proteins encoded by Gag and Pol are not subject to TRIM5alpha-mediated accelerated degradation. The accelerated CA degradation by TRIM5alpha apparently occurs via a nonproteosomal pathway. TRIM5alpha selectively accelerates degradation of the CA population, which reached the cytosol of restrictive cells, but not the CA population, which ended into the vesicular compartment. Given that cytosolic CA represents "productively" entered cores, whereas vesicular CA represents "nonproductively" entered cores, our findings suggest that TRIM5alpha interrupts the infectious pathway of HIV-1 by acting on the incoming cytosolic CA. The mode of viral entry does not influence the accelerated degradation of cytosolic CA by TRIM5alpha. Thus, this study reveals a correlation between TRIM5alpha-mediated HIV-1 restriction and a selective degradation of cytosolic CA normally associated with productive viral entry.
Chatterji
Udayan
U
Departments of Immunology, Molecular and Integrative Neurosciences, and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Bobardt
Michael D
MD
Gaskill
Peter
P
Sheeter
Dennis
D
Fox
Howard
H
Gallay
Philippe A
PA
D000818:Animals; D000090103:Antiviral Restriction Factors; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002213:Capsid / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism / Q000821:virology*; D015683:Gene Products, gag / Q000378:metabolism; D015684:Gene Products, pol / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D015683:Gene Products, gag; D015684:Gene Products, pol; D011506:Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex