[14] The TRIM5α, once formed into its highly regular reticulatory net recruits ubiquitin for this purpose, which, in turn engages the proteasome.

[17][18] TRIM5α may have played a critical role in the human immune defense system about 4 million years ago, when the retrovirus PtERV1 was infecting the ancestors of modern chimpanzees.

While this cellular defense mechanism may have been very useful 4 million years ago when facing a PtERV1 epidemic, it has the side effect of leaving cells more susceptible to attack by the HIV-1 retrovirus.

By using a PtERV1 capsid, which produces higher titer virus-like particles, Perez-Caballero et al. reported that PtERV1 is not restricted by either human or chimpanzee TRIM5α.

[19] Rhesus macaques, a species of Old World monkeys, appeared to be almost completely resistant to HIV-1, the virus that causes AIDS in humans.

[26][27] It was recently described that interferon-α-mediated stimulation of the immunoproteasome enables human TRIM5α for effective capsid-dependent inhibition of HIV-1 DNA synthesis and infection.