Abstract
The delivery of the HIV-1 genome into the nucleus is an indispensable step in retroviral infection of non-dividing cells, but the mechanism of HIV-1 nuclear import has been a longstanding debate due to controversial experimental evidence. It was commonly believed that the HIV-1 capsid would need to disassemble (uncoat) in the cytosol before nuclear import because the capsid is larger than the central channel of nuclear pore complexes (NPCs); however, increasing evidence demonstrates that intact, or nearly intact, HIV-1 capsid passes through the NPC to enter the nucleus. With the protection of the capsid, the HIV-1 core completes reverse transcription in the nucleus and is translocated to the integration site. Uncoating occurs while, or after, the viral genome is released near the integration site. These independent discoveries reveal a compelling new paradigm of this important step of the HIV-1 life cycle. In this review, we summarize the recent studies related to HIV-1 nuclear import, highlighting the spatial–temporal relationship between the nuclear entry of the virus core, reverse transcription, and capsid uncoating.
Highlights
HIV-1 (AIDS) remains a worldwide threat to human health and society
Recent research advances have led to an emerging picture of the HIV-1 core entering the nucleus with an intact or largely intact capsid (Figure 4B), many details still need to be elucidated
Multiple copies of NUP358 filaments of the nuclear pore complexes (NPCs) capture the capsid from the cytosol, and facilitate docking of the virus core on the NPC
Summary
HIV-1 (AIDS) remains a worldwide threat to human health and society. As a retrovirus, the delivery of the viral genome to the nucleus is a necessary step in the infection process [1]. The capsid may disassemble within 15 min, near the integration site (Figure 2) [13,20] These data indicate that a successful HIV infection requires a virus core that: (1) travels to the NPC along microtubule networks with an intact capsid and conducts RT in the capsid; (2) docks to and passes through the NPC into the nucleus with an intact or largely intact capsid; (3) reaches nuclear speckles while completing RT; (4) rapidly uncoats near the integration site and releases viral DNA. The Diameter of the NPC’s Central Channel Can Dilate to ~64 nm NPCs act as gatekeepers at the nuclear envelope, where they control the bidirectional exchange of molecules between the compartments of the nucleus and the cytoplasm [31,32] They are the only known gateway for HIV-1 to deliver its viral genome into the nucleus and infect non-dividing cells [1,33]. Whether the ~64 nm width of the central channel is universal and reflects its natural state on other types of eukaryotic cells is still unknown; a recent report showed that intact HIV-1 capsid was detected in the nucleus of a wide range of cells beside SupT1-R5 [22]
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