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Review
. 2021 Dec 30;17(12):e1010109.
doi: 10.1371/journal.ppat.1010109. eCollection 2021 Dec.

HIV-1 capsid is the key orchestrator of early viral replication

Vojtech Zila  1 , Thorsten G Müller  1 , Barbara Müller  1 , Hans-Georg Kräusslich  1   2
Affiliations
Review

HIV-1 capsid is the key orchestrator of early viral replication

Vojtech Zila et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Early postentry steps of HIV-1 replication.
(A) After fusion-mediated release of the HIV-1 capsid into the cytosol, reverse transcription of the viral RNA genome into double-stranded cDNA commences (RTC), and the capsid interacts with dynein and kinesin-1 motor complexes for transport along MTs toward the nuclear envelope (reviewed in [14]). (B) At the cytosolic side of NPCs, MT-associated capsids encounter Nup358 (blue rectangles), a major component of filaments emanating from the NPC. After docking at the nuclear pore with their narrow end, capsids then penetrate into the NPC central channel, which is sufficiently dilated to accommodate the complete capsid. (C) Once exposed to the nucleoplasm, sequential interaction of the CA lattice with Nup153 (blue dots) and CPSF6 (green dots) (and possibly other factors) releases the capsid into the nucleoplasm. CPSF6 mediates accumulation of capsids in NSs, where cDNA synthesis is completed (i). Inside the nucleus, the capsid structure is physically disrupted and the PIC is released (ii). (D) The PIC then separates from the capsid remnants (iii) and integrates into the host cell genome in SPADs or SE domains (reviewed in [10,31]). (E) In the absence of CPSF6, the capsid remains close to the nuclear basket and does not efficiently enter the nucleoplasm. Completion of cDNA synthesis and uncoating occur at this site, followed by breakage of the capsid and genome integration into LADs [10]. CA, capsid protein; HIV-1, human immunodeficiency virus 1; LAD, lamin-associated domain; MT, microtubule; MTOC, microtubule organizing center; NE, nuclear envelope; NPC, nuclear pore complex; NS, nuclear speckle; PIC, preintegration complex; RTC, reverse transcription complex; SE, super-enhancer-rich domain; SPAD, speckle-associated domain.
Fig 2
Fig 2. Nuclear import of HIV-1 CA visualized by ET.
Three-dimensional rendering of electron tomographic reconstruction shows the HIV-1 capsid penetrating the NPC central channel in an infected T lymphoblast. ET, electron tomography; HIV-1, human immunodeficiency virus (1); NE, nuclear envelope; NPC, nuclear pore complex; MT, microtubule. Adapted from Lucic and colleagues [31].
See this image and copyright information in PMC

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