Abstract
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural changes in the nuclear envelope, and is completed by intranuclear disassembly of capsids and chromatinization of the viral genome. This review discusses the nuclear import strategies of protoparvoviruses and describes its dynamics comprising active and passive movement, and directed and diffusive motion of capsids in the molecularly crowded environment of the cell.
Highlights
DNA viruses, and some RNA viruses, such as retroviruses, orthomyxoviruses and bornaviruses, have to enter the cell nucleus due to their need of the nuclear DNA replication and transcription machinery
After the stepwise endosomal uptake, CPV and other parvoviruses, including adeno-associated virus 2 (AAV2), a member of the genus dependoparvovirus, are present in small vesicles scattered around the cytoplasm, and in large vesicles accumulated in the perinuclear area [30,39,40,41,42,43]
The import reaction is terminated in the nuclear basket where the cargo-import receptor-complex binds to Nup153 [91]. This leads to dissociation of import receptor from its cargo, a process induced by GTP-bound form of Ras-related nuclear protein (Ran) [92,93]
Summary
DNA viruses (with exception of poxviridae family), and some RNA viruses, such as retroviruses, orthomyxoviruses and bornaviruses, have to enter the cell nucleus due to their need of the nuclear DNA replication and transcription machinery Their genomes have to be transported from the cell periphery into the nucleus facilitated by multiple coordinated interactions between the virus (or a subviral structure) and host proteins. VP3 is the smallest capsid protein formed by a 15 to 20 aa cleavage from the N-terminus of VP2 It is only found in mature DNA-containing capsids, where its ratio with VP2 defines the virus species and maturity [25,26]. Nuclear import of capsids and their disassembly are followed by genome replication and viral assembly, which require the import of structural and nonstructural viral proteins
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