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  2. Highly pathogenic H7N9 avian influenza virus infection associated with up-regulation of PD-1/PD-Ls pathway-related molecules

Highly pathogenic H7N9 avian influenza virus infection associated with up-regulation of PD-1/PD-Ls pathway-related molecules

  • Int Immunopharmacol. 2020 Aug;85:106558. doi: 10.1016/j.intimp.2020.106558.
Yan Hua Li 1 Chen Yu Hu 1 Lin Fang Cheng 1 Xiao Xin Wu 1 Tian Hao Weng 1 Nan Ping Wu 1 Hang Ping Yao 2 Lan Juan Li 3
Affiliations

Affiliations

  • 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310031, China.
  • 2 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310031, China. Electronic address: [email protected].
  • 3 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310031, China. Electronic address: [email protected].
Abstract

To investigate the main transcriptional and biological changes of human host during low and highly pathogenic avian H7N9 Influenza Virus infection and to analyze the possible causes of escalated virulence and the systematic progression of H7N9 virus Infection, we utilized whole transcriptome sequencing (RNA-chip and RNA-seq) and other biomolecular methods to analyze and verify remarkable changes of host cells during these two subtypes of H7N9 influenza viruses Infection. Whole transcriptome analysis showed the global profiles of differentially expressed genes (DEGs) and identified 458 DEGs associated with major changes in biological processes of the host cells after Infection with 2017 HPAI H7N9 virus versus 2013 LPAI H7N9 virus, mainly including drastically increased defense responses to viruses (e.g. negative regulation of viral gene replication), IFNs related pathways, immune response/native immune response, and inflammatory response. Genes of programmed cell death 1 (PD-1) pathways were found changed remarkably and several highly correlated non-coding RNAs were identified. The results suggested that HPAI H7N9 virus induces stronger immune response and suppressing response than LPAI H7N9. Meanwhile, PD-1/PD-Ls signaling pathways work together in regulating host responses including Antiviral defense, lethal inflammation caused by the virus and immune response, thus contribute to the high pathogenicity of 2017H7N9 virus that can be regulated by non-coding RNAs. The present study represents a comprehensive understanding and good reference of regulation of pathogenicity of H7N9 virus even other fatal viruses and correlated host immune responses.

Keywords

Antiviral immune response; H7N9; Highly pathogenic avian influenza; PD-1; PD-L1; PD-L2.

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