Since SEC24C, NUP153 and CPSF6 are predominantly present in the cytoplasm, the NPC and the nucleus, respectively, we suggest that the avid prion-like LCR mediated virus-host interactions are utilized throughout early steps of infection to enable HIV-1 to effectively traffic across the cytoplasm, transit the NPC, and complete the journey inside the nucleus to integrate into chromatin. Here, NUP153 is linked to infection.