As a retrovirus, HIV needs to deliver its genome to the nucleus and reverse transcribe it before integration. There is a longstanding debate, with various, often contradictory results, about when and where the capsid that surrounds the HIV genome disassembles, that is, ‘uncoats’. Burdick et al. now suggest that uncoating only happens after HIV has entered the nucleus and reverse transcribed its genome, delivering it close to integration sites. They labelled capsid with GFP by inserting the fluorescent marker between matrix and capsid and mutating a protease cleavage site to avoid loss of the marker. When they tracked labelled viral cores, they found, in contrast to previous studies that had suggested uncoating in the cytoplasm, that cores remained intact or nearly intact until they had reached their nuclear destination. Furthermore, their results suggest that interaction with the host protein cleavage and polyadenylation specificity factor 6 supports entry through nuclear pores. Once in the nucleus, reverse transcription happened inside the cores, and viral DNA was only released shortly before integration, potentially protecting it from innate DNA sensing.
Burdick, R. C. et al. HIV-1 uncoats in the nucleus near sites of integration. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.1920631117 (2020)
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Hofer, U. Entering and breaking for HIV?. Nat Rev Microbiol 18, 264 (2020). https://doi.org/10.1038/s41579-020-0352-9