Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus
Dong-Shan Yu1,2, Xiao-Xin Wu1, Tian-Hao Weng1
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310003, PR China.
Abstract:
Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.
Insights
Researchers identified 12 host proteins crucial for highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection. These interactions offer new targets for developing antiviral therapies against HPAI H7N9.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Host-virus interactions are critical for viral replication and disease but are poorly understood for highly pathogenic avian influenza A virus H7N9 (HPAI H7N9).
- Identifying specific host factors involved in HPAI H7N9 infection is essential for understanding viral pathogenesis and developing effective treatments.
Purpose of the Study:
- To identify host factors and their interactions with viral proteins during HPAI H7N9 infection.
- To investigate the role of these host-viral protein interactions in the HPAI H7N9 life cycle.
- To discover novel host-viral interactions specific to HPAI H7N9 compared to other influenza A viruses (IAVs).
Main Methods:
- Designed and synthesized 65 small interfering RNAs (siRNAs) targeting host genes.
- Employed RNA interference (RNAi) screening to identify host factors involved in HPAI H7N9 replication.
- Utilized co-immunoprecipitation assays to assess interactions between viral and host proteins.
Main Results:
- Identified 12 key host proteins: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), AP3S1, ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COPA), COPG1, heat shock protein family A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18.
- Confirmed intricate interactions between viral proteins (hemagglutinin, matrix 1, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and the identified host proteins.
- Discovered novel interactions between HPAI H7N9 proteins and ANXA5, AP2S1, AP3S1, ATP5A1, HSP90AA1, and RAB18, distinguishing it from other IAVs.
Conclusions:
- Host-viral protein interactions significantly influence HPAI H7N9 infection dynamics.
- Specific host factors and their interactions represent potential targets for novel antiviral strategies.
- Understanding these interactions provides insights into HPAI H7N9 pathogenesis and variations among IAVs.
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