A putative mechanism for restriction of retroviruses by TRIM5α. (Panel A) TRIM5α is autoubiquitinylated in a RING dependent way and rapidly turned over by the proteasome . If it encounters incoming sensitive retroviral cores then they too are recruited to the proteasome and destroyed, before the virus has the opportunity for significant reverse transcription. (Panel B) If the virus/TRIM5α complex is protected from destruction, by inhibiting the proteasome, then the virus can reverse transcribe [48, 49]. Infectivity is not rescued however, indicating that the virus/TRIM5α complex is uninfectious. How TRIM5 renders the virus uninfectious remains unclear.