Characterization of the nuclear localization sequence of beak and feather disease virus capsid proteins and their assembly into virus-like particles

Chen, Jui-Kai; Hsiao, Chiaolong; Lo, An-Ru; Wang, Chi-Young

doi:10.1016/j.virusres.2020.198144

Cited by 5 publications

(9 citation statements)

References 32 publications

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“…Whether the NLS and the DNAbinding region are functionally coupled or act independently is yet to be determined. In addition to classical nuclear import pathways, PCV2 Cap has also been reported to recruit dynein for transport to the nucleus through the dynein/microtubule machinery (12). In this model PCV2 Cap subunits might act as a direct ligand of the cytoplasmic dynein IC1 subunit and an inducer of microtubule a-tubulin acetylation, which enhances intracellular transport (12).…”

Section: Circovirus Capsid Structuresmentioning

confidence: 99%

“…The extracellular matrix component heparan sulfate (HS) has been shown to be bound by circovirus capsids (19) with this proteoglycan likely acting as a key cell receptor, as blocking of Cap:HS interaction with the small molecule epigallocatechin gallate prevents PCV2 uptake (42). Following attachment to the cell surface, circovirus virions are internalized, with evidence suggesting that this is mediated by an ATP-and caveolin-dependent process for BFDV and clathrin-or actin and small GTPase dependent for PCV2 (12,57). Although the details of the endocytosis and vesicular transport of circoviruses remain elusive, it is known that these viruses are able to cross bilayer membranes to enter the cytoplasm; presumably through the action of a cell-penetrating peptide (97).…”

Section: The Replication Cycle Of Circovirusesmentioning

confidence: 99%

“…Although the details of the endocytosis and vesicular transport of circoviruses remain elusive, it is known that these viruses are able to cross bilayer membranes to enter the cytoplasm; presumably through the action of a cell-penetrating peptide (97). From the cytoplasm, viral Cap proteins interact with the host importin receptors through nuclear localization signal (NLS) motifs for transport into the nuclear lumen (12,97). Within the nucleus, circovirus ssDNA genomes dissociate from viral capsids, interact with host polymerase factors, and enter rolling circle replication (RCR) (57).…”

Section: The Replication Cycle Of Circovirusesmentioning

confidence: 99%

“…The N-terminus of the Cap protein contains NLSs for mediating transfer of this protein and the associated genomic DNA into the host cell nucleus (29). Both the NLSs, and antagonizing nuclear export signals, have been identified on the Cap protein of BFDV, and shown to be critical for nuclear entry and exit, respectively, in vitro (12). The NLS region is also responsible for binding the ssDNA genome.…”

Section: Cap Proteinmentioning

confidence: 99%

“…In addition to classical nuclear import pathways, PCV2 Cap has also been reported to recruit dynein for transport to the nucleus through the dynein/microtubule machinery (12). In this model PCV2 Cap subunits might act as a direct ligand of the cytoplasmic dynein IC1 subunit and an inducer of microtubule a-tubulin acetylation, which enhances intracellular transport (12). The ARM sequences of circoviruses also play an important role in regulating genome encapsidation (15,35).…”

Section: Circovirus Capsid Structuresmentioning

confidence: 99%

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Structural Perspectives of Beak and Feather Disease Virus and Porcine Circovirus Proteins

et al. 2021

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Circoviruses represent a rapidly expanding group of viruses that infect both vertebrate and invertebrate hosts. Members are responsible for diseases of veterinary and economic importance, including postweaning multisystemic wasting syndrome in pigs, and beak and feather disease (BFD) in birds. These viruses are associated with lymphoid depletion and immunosuppressive conditions in infected animals leading to systemic illness. Circoviruses are small nonenveloped DNA viruses containing a single-stranded circular genome, encoding two major proteins: the capsid-associated protein (Cap), comprising the entirety of the viral capsid, and the replication-associated protein (Rep). Cap is the only protein component of the virion and plays crucial roles throughout the virus replication cycle, including viral attachment, cell entry, genome uncoating, and packaging of newly formed viral particles. Rep mediates recognition of replication origin motifs in the viral genome sequence and is responsible for endonuclease activity enabling nicking of the circular DNA and initiation of rolling-circle replication (RCR). Porcine circovirus 2 (PCV2) was the first circovirus capsid structure to be solved at atomic resolution using X-ray crystallography. The structure revealed an assembly comprising 60 monomeric subunits to form virus-like particles. Each Cap monomer harbors a canonical viral jelly roll domain composed of two, four-stranded antiparallel b-sheets. Crystal structures of two distinct macromolecular assemblies from BFD virus Cap were also resolved at high resolution. In these structures, the exposure of the N-terminal arginine-rich motif, responsible for DNA binding and nuclear localization is reversed. Additional structural investigations have also elucidated a PCV2 type-specific neutralizing epitope, and interaction between the PCV2 capsid and polymers such as heparin. In this review, we provide a snapshot of the structural and functional aspects of circovirus proteins.

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Section: Circovirus Capsid Structuresmentioning

confidence: 99%