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Open AccessArticle

A Mechanism Underlying Attenuation of Recombinant Influenza A Viruses Carrying Reporter Genes

by Xiujuan Zhao 1,†, Lin Wang 1,†, Qinghua Cui 1,2, Ping Li 1, Yanyan Wang 1, Yingying Zhang 2,3, Yong Yang 2,4, Lijun Rong 5,* and Ruikun Du 1,2,*
1
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
2
Shandong Provincial Collaborative Innovation Center for Antiviral Traditional Chinese Medicine, Jinan 250355, China
3
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
4
Scientific Research Centre, College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
5
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
*
Authors to whom correspondence should be addressed.
These authors contribute equally to this work.
Viruses 2018, 10(12), 679; https://doi.org/10.3390/v10120679
Received: 22 October 2018 / Revised: 27 November 2018 / Accepted: 27 November 2018 / Published: 30 November 2018
(This article belongs to the Section Animal Viruses)
Influenza A viruses (IAV) carrying reporter genes provide a powerful tool to study viral infection and pathogenesis in vivo, however, incorporating a non-essential gene into the IAV genome often results in virus attenuation and genetic instability. Very few studies have systematically compared different reporter IAVs, and most optimization attempts seem to lack authentic directions. In this study, we evaluated the ratio of genome copies to the number of infectious unit of two reporter IAVs, PR8-NS1-Gluc and PR8-PB2-Gluc. As a result, PR8-NS1-Gluc and PR8-PB2-Gluc produced 41.4 and 3.8 genomes containing noninfectious particles respectively for every such particle produced by parental PR8 virus. RdRp assay demonstrated that modification of segment NS by inserting reporter genes can interfere with the replication competitive property of the corresponding vRNAs, and the balance of the 8 segments of the reporter IAVs were drastically impaired in infected cells. As a consequence, large amounts of NS-null noninfectious particles were produced during the PR8-NS1-Gluc packaging. In summary, we unravel a mechanism underlying attenuation of reporter IAVs, which suggests a new approach to restore infectivity and virulence by introducing extra mutations compensating for the impaired replication property of corresponding segments. View Full-Text
Keywords: influenza A virus; reporter virus; attenuation; mechanism; noninfectious particles; vRNA replication influenza A virus; reporter virus; attenuation; mechanism; noninfectious particles; vRNA replication
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MDPI and ACS Style

Zhao, X.; Wang, L.; Cui, Q.; Li, P.; Wang, Y.; Zhang, Y.; Yang, Y.; Rong, L.; Du, R. A Mechanism Underlying Attenuation of Recombinant Influenza A Viruses Carrying Reporter Genes. Viruses 2018, 10, 679.

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