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Article

Impaired Nuclear Export of the Ribonucleoprotein Complex and Virus-Induced Cytotoxicity Combine to Restrict Propagation of the A/Duck/Malaysia/02/2001 (H9N2) Virus in Human Airway Cells

by
Sriram Kumar
1,
Dawn Yeo
1,2,
Nisha Harur Muralidharan
1,
Soak Kuan Lai
1,
Cathlyn Tong
1,
Boon Huan Tan
2 and
Richard J. Sugrue
1,*
1
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
2
Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510, Singapore
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 355; https://doi.org/10.3390/cells9020355
Submission received: 8 November 2019 / Revised: 20 January 2020 / Accepted: 29 January 2020 / Published: 3 February 2020
(This article belongs to the Special Issue Host–Pathogen Interactions During Influenza Virus Infection)
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Abstract

In humans, (A549) cells impaired H9N2 virus nuclear export of the ribonucleoprotein (RNP) complex contrasted with the early and efficient nuclear export of the H1N1/WSN and pH1N1 virus RNP complexes. Although nuclear export of the RNP complex occurred via the nuclear pore complex, H9N2 virus infection also induced modifications in the nuclear envelope and induced cell cytotoxicity. Reduced PA protein levels in H9N2 virus-infected A549 cells occurred, and this phenomenon was independent of virus infection. Silencing the H1N1/WSN PA protein expression leads to impaired nuclear export of RNP complexes, suggesting that the impaired nuclear export of the H9N2 virus RNP complex may be one of the consequences of reduced PA protein levels. Early and efficient export of the RNP complex occurred in H9N2 virus-infected avian (CEF) cells, although structural changes in the nuclear envelope also occurred. Collectively our data suggest that a combination of delayed nuclear export and virus-induced cell cytotoxicity restricts H9N2 virus transmission in A549 cells. However, the early and efficient export of the RNP complex mitigated the effects of virus-induced cytotoxicity on H9N2 virus transmission in CEF cells. Our findings highlight the multi-factorial nature of host-adaptation of the polymerase proteins of avian influenza viruses in non-avian cell environments.
Keywords: avian influenza virus; H9N2 virus; nucleoprotein; ribonucleoprotein (RNP) complex; PA protein; lamin A/C avian influenza virus; H9N2 virus; nucleoprotein; ribonucleoprotein (RNP) complex; PA protein; lamin A/C

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MDPI and ACS Style

Kumar, S.; Yeo, D.; Harur Muralidharan, N.; Lai, S.K.; Tong, C.; Tan, B.H.; Sugrue, R.J. Impaired Nuclear Export of the Ribonucleoprotein Complex and Virus-Induced Cytotoxicity Combine to Restrict Propagation of the A/Duck/Malaysia/02/2001 (H9N2) Virus in Human Airway Cells. Cells 2020, 9, 355. https://doi.org/10.3390/cells9020355

AMA Style

Kumar S, Yeo D, Harur Muralidharan N, Lai SK, Tong C, Tan BH, Sugrue RJ. Impaired Nuclear Export of the Ribonucleoprotein Complex and Virus-Induced Cytotoxicity Combine to Restrict Propagation of the A/Duck/Malaysia/02/2001 (H9N2) Virus in Human Airway Cells. Cells. 2020; 9(2):355. https://doi.org/10.3390/cells9020355

Chicago/Turabian Style

Kumar, Sriram, Dawn Yeo, Nisha Harur Muralidharan, Soak Kuan Lai, Cathlyn Tong, Boon Huan Tan, and Richard J. Sugrue. 2020. "Impaired Nuclear Export of the Ribonucleoprotein Complex and Virus-Induced Cytotoxicity Combine to Restrict Propagation of the A/Duck/Malaysia/02/2001 (H9N2) Virus in Human Airway Cells" Cells 9, no. 2: 355. https://doi.org/10.3390/cells9020355

APA Style

Kumar, S., Yeo, D., Harur Muralidharan, N., Lai, S. K., Tong, C., Tan, B. H., & Sugrue, R. J. (2020). Impaired Nuclear Export of the Ribonucleoprotein Complex and Virus-Induced Cytotoxicity Combine to Restrict Propagation of the A/Duck/Malaysia/02/2001 (H9N2) Virus in Human Airway Cells. Cells, 9(2), 355. https://doi.org/10.3390/cells9020355

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