Journal
VIRUSES-BASEL
Volume 14, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/v14071402
Keywords
avian metapneumovirus subgroup C; fusion (F) protein; NCL; AS1411; replication
Categories
Funding
- National Natural Science Foundation [31830095]
- China Agriculture Research System [CARS-41]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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It has been found that avian metapneumovirus subgroup C (aMPV/C) infection can cause changes in the subcellular localization of nucleolin (NCL) and NCL plays a role in aMPV/C replication. Knocking down NCL using siRNA or CRISPR/Cas9 significantly reduces aMPV/C replication, while overexpression of NCL increases viral replication. The interaction between the aMPV/C fusion (F) protein and NCL is important for viral replication, and AS1411 disrupts this interaction, inhibiting aMPV/C replication.
Avian metapneumovirus subgroup C (aMPV/C) is highly pathogenic to various avian species with acute respiratory tract clinicopathology and/or drops in egg production. Nucleolin (NCL), an important nucleolar protein, has been shown to regulate multiple viral replication and serve as a functional receptor for viral entry and internalization. Whether NCL is involved in aMPV/C pathogenesis is not known. In this study, we found that aMPV/C infection altered the subcellular localization of NCL in cultured cells. siRNA-targeted NCL resulted in a remarkable decline in aMPV/C replication in Vero cells. DF-1 cells showed a similar response after CRISPR/Cas9-mediated knock out of NCL during aMPV/C infection. Conversely, NCL overexpression significantly increased aMPV/C replication. Pretreatment with AS1411-a aptamer, a guanine (G)-rich oligonucleotide that forms four-stranded structures and competitively binding to NCL, decreased aMPV/C replication and viral titers in cultured cells. Additionally, we found that the aMPV/C fusion (F) protein specifically interacts with NCL through its central domain and that AS1411 disrupts this interaction, thus inhibiting viral replication. Taken together, these results reveal that the aMPV/C F protein interacts with NCL, which is employed by aMPV/C for efficient replication, thereby highlighting the strategic potential for control and therapy of aMPV/C infection.
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