A model for cofactor use during HIV-1 reverse transcription and nuclear entry

•HIV-1 utilises CPSF6 to suppress premature reverse transcription and target viral cores to nuclear pores.•HIV-1 uses TNPO3 to transport the preintegration complex into the nucleus.•HIV-1 uses this pathway to target active chromatin whilst evading innate sensors. Lentiviruses have evolved to infect and replicate in a variety of cell types in vivo whilst avoiding the powerful inhibitory activities of restriction factors or cell autonomous innate immune responses. In this review we offer our opinions on how HIV-1 uses a series of host proteins as cofactors for infection. We present a model that may explain how the capsid protein has a fundamental role in the early part of the viral lifecycle by utilising cyclophilin A (CypA), cleavage and polyadenylation specificity factor-6 (CPSF6), Nup358 and TNPO3 to orchestrate a coordinated process of DNA synthesis, capsid uncoating and integration targeting that evades innate responses and promotes integration into preferred areas of chromatin.