Not long after the initial discovery of TRIM5 as a retroviral restriction factor, it was demonstrated that the restriction of HIV-1 infection in owl monkey cells is caused by the expression of an unusual fusion protein made up of the N-terminal R-B-CC domains of TRIM5 and a cyclophilin A (CypA) domain at the C-terminus20,21. Here, TRIM5 is linked to HIV-1 infection.