Saturation of TRIM5 alpha-mediated restriction of HIV-1 infection depends on the stability of the incoming viral capsid.
HIV-1 infection is restricted at a post-entry stage in some simian cell lines by species-specific variants of TRIM5 alpha. Restriction targets the viral capsid protein (CA) and results in attenuated reverse transcription. TRIM5 alpha restriction can be inhibited by the addition of noninfectious virus-like particles (VLPs), thus rendering cells permissive for infection by an HIV-1 reporter virus. Through the use of HIV-1 VLPs containing Gag cleavage site substitutions and point mutations in CA which alter the stability of the viral capsid, we demonstrate that saturation of TRIM5 alpha restriction depends on the stability of the capsid in the incoming VLPs. Differences in the requirement for cleavage of the specific sites in Gag were observed between distinct African green monkey cell lines. The results strongly suggest that the mechanism of HIV-1 restriction by TRIM5 alpha involves engagement of the viral capsid by the restriction factor prior to completion of uncoating.
Shi
Jiong
J
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, A-5301 Medical Center North, Nashville, TN 37232-2363, USA.
Aiken
Christopher
C
D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D011533:Proviruses / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors / Q000502:physiology
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; D014760:Viral Fusion Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases