Structural and functional characterization of siadenovirus core protein VII nuclear localization demonstrates the existence of multiple nuclear transport pathways

Athukorala, Ajani, Donnelly, Camilla M., Pavan, Silvia, Nematollahzadeh, Sepehr, Djossou, Victoria Atalie, Nath, Babu, Helbig, Karla J., Di Iorio, Enzo, McSharry, Brian P., Alvisi, Gualtiero, Forwood, Jade K., and Sarker, Subir (2024) Structural and functional characterization of siadenovirus core protein VII nuclear localization demonstrates the existence of multiple nuclear transport pathways. Journal of General Virology, 105 (1). 001928.

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Adenovirus protein VII (pVII) plays a crucial role in the nuclear localization of genomic DNA following viral infection and contains nuclear localization signal (NLS) sequences for the importin (IMP)-mediated nuclear import pathway. However, functional analysis of pVII in adenoviruses to date has failed to fully determine the underlying mechanisms responsible for nuclear import of pVII. Therefore, in the present study, we extended our analysis by examining the nuclear trafficking of adenovirus pVII from a non-human species, psittacine siadenovirus F (PsSiAdV). We identified a putative classical (c)NLS at pVII residues 120-128 (120PGGFKRRRL128). Fluorescence polarization and electrophoretic mobility shift assays demonstrated direct, high-affinity interaction with both IMPα2 and IMPα3 but not IMPβ. Structural analysis of the pVII-NLS/IMPα2 complex confirmed a classical interaction, with the major binding site of IMPα occupied by K124 of pVII-NLS. Quantitative confocal laser scanning microscopy showed that PsSiAdV pVII-NLS can confer IMPα/β-dependent nuclear localization to GFP. PsSiAdV pVII also localized in the nucleus when expressed in the absence of other viral proteins. Importantly, in contrast to what has been reported for HAdV pVII, PsSiAdV pVII does not localize to the nucleolus. In addition, our study demonstrated that inhibition of the IMPα/β nuclear import pathway did not prevent PsSiAdV pVII nuclear targeting, indicating the existence of alternative pathways for nuclear localization, similar to what has been previously shown for human adenovirus pVII. Further examination of other potential NLS signals, characterization of alternative nuclear import pathways, and investigation of pVII nuclear targeting across different adenovirus species is recommended to fully elucidate the role of varying nuclear import pathways in the nuclear localization of pVII.

Item ID: 82063
Item Type: Article (Research - C1)
ISSN: 1465-2099
Keywords: adenovirus protein VII, importin α/β-mediated nuclear import, nuclear localization, psittacine siadenovirus F
Copyright Information: © 2024 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Funders: Australian Research Council (ARC)
Projects and Grants: ARC DE200100367
Date Deposited: 21 Mar 2024 05:09
FoR Codes: 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310706 Virology @ 100%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280101 Expanding knowledge in the agricultural, food and veterinary sciences @ 50%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 50%
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