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

A molecular switch modulates assembly and host factor binding of the HIV-1 capsid

“…This finding reinforces the importance of the assembled capsid lattice in the nuclear import process. Other studies indicate that pentamer-specific factors might facilitate core trafficking or docking to the nucleus 3,38 , pointing to division of labor between the two capsomers and supporting the requirement for an intact or nearly intact capsid at these viral replication steps.…”

“… Abstract Upon entry into a new host cell, the HIV-1 capsid performs multiple essential functions, which include shielding the genome from innate immune sensors 1 , promoting reverse transcription 2 and transporting the core from the entry site at the plasma membrane to the integration site inside the nucleus 3,4 . The HIV-1 capsid is a fullerene cone made of hexamers and pentamers of the viral CA protein 5,6 .…”

HIV Capsid Protein Genetic Diversity Across HIV-1 Variants and Impact on New Capsid-Inhibitor Lenacapavir

“…Although previous models pointed to an early cytoplasmatic capsid disassembly ( Miller et al, 1997 ; Mamede et al, 2017 ), recent studies have supported the possibility of a complete or almost intact capsid entering the nucleus ( Burdick et al, 2020 ; Dharan et al, 2020 ; Li et al, 2021 ; Zila et al, 2021a ). Increasing evidence suggests that the capsid participates in the translocation of viral genomic material into the host nucleus for integration through partial uncoating that allows higher plasticity of the capsid, through structural rearrangements of the nuclear pore, or by both mechanisms ( Dharan et al, 2020 ; Toccafondi et al, 2021 ; Zhuang and Torbett, 2021 ; Zila et al, 2021b ).…”

“…In addition to this structural function, the capsid is involved in different steps of the viral infectious cycle, such as HIV reverse transcription (RT), cytoplasmic trafficking through microtubules, decapsidation and nuclear import of the viral pre-integration complex, integration, and assembly ( Sundquist and Kräusslich, 2012 ; Campbell and Hope, 2015 ; Novikova et al, 2019 ; Engelman, 2021 ; Zila et al, 2021b ). Recent in vitro studies suggest that the capsid plays a key role in HIV RT contributing directly to its efficiency, maintaining sufficient concentrations of RT, and other core components needed for the long process of RT, excluding cytoplasmatic molecules that may degrade the viral nucleic acids, and interacting with certain molecules, such as IP6 (inositol-hexakisphosphate), which enhances RT in vitro by stabilizing the viral capsid ( Mallery et al, 2018 ; Christensen et al, 2020 ; Aiken and Rousso, 2021 ).…”

Direct capsid labeling of infectious HIV-1 by genetic code expansion allows detection of largely complete nuclear capsids and suggests nuclear entry of HIV-1 complexes via common routes

“…The cone-shaped capsid that encases the viral RNA genome and replication proteins is a characteristic feature of infectious human immunodeficiency virus type 1 (HIV-1) particles. Data obtained by many research groups over the past decade have revised our understanding of the role of the mature capsid in HIV-1 replication, placing this structure at the center stage of post-entry replication steps (reviewed in (Aiken and Rousso, 2021; Engelman, 2021; James, 2019; Zila et al, 2021b). Upon fusion of the virion envelope with the cell membrane, the capsid, which consists of ∼1,200-1,500 monomers of the capsid protein CA (Briggs et al, 2003), is released into the cytosol.…”