During the long-term evolutionary history, the interaction between virus and host has driven the first-line barrier, innate immunity, to invading pathogens. Innate immune factor TRIM5α and host peptidyl-prolyl cis-trans isomerase Cyclophilin A are two key players in the interaction between HIV-1 and host. Interestingly, Cyclophilin A is retrotransposed into the critical host gene, TRIM5, locus via LINE-1 element in some primate species including New World monkeys and Old World monkeys. This review aims to comprehensively discuss the sensing and immune activation procedures of TRIM5α innate signaling pathway through Cyclophilin A. It will then present the production of TRIMCyp chimeric gene and the different fusion patterns in primates. Finally, it will summarize the distinct restriction activity of TRIMCyp from different primates and explain the current understanding on the innate immune mechanisms involved in the early phase of the viral life cycle during HIV-1 replication.