Over the past decade, the role of the mature HIV-1 capsid in viral replication has undergone a major paradigm shift. It became increasingly clear that the simple view of the capsid as a mere proteinaceous wrapper encasing the viral genome, which becomes obsolete soon after cytosolic entry, is incorrect. Today it is no longer debated that not only the CA protein but the capsid itself is involved in post-entry events subsequent to cytosolic entry. However, its precise function is incompletely understood and such questions as ‘when, where, and how does capsid uncoating occur?’ are controversially discussed. This presentation focuses on modern fluorescent labeling and imaging approaches that contribute to our current understanding of post-entry events and the fate and functions of the viral capsid. Recent work from several laboratories has shed light on pathways and mechanisms involved in trafficking of viral complexes to and through the nuclear pore, resulting in emergence of the assembled capsid as a master organizer of HIV-1 post entry. It mediates numerous interactions with the host cell environment, acting as a reaction container, as a protective shield around the nascent viral DNA, and as a transport vehicle that mediates targeted transfer of subviral complexes, from the site of cytosolic entry to integration of the proviral DNA in the host cell nucleus. Although open questions remain, recent studies from us and others have begun to resolve apparent discrepancies that had led to discordant conclusions in the past. Theese studies open the door toward a clear understanding of molecular events during the post-entry phase of HIV-1 replication.
CROI Conference
