Recruitment of RED-SMU1 Complex by Influenza A Virus RNA Polymerase to Control Viral mRNA Splicing


Influenza A viruses are major pathogens which pose continuous animal and public health challenges. Enhancing the knowledge of their life cycle, and especially the understanding of how viral components interact with the host cell, is essential to achieve better prevention and treatment of the disease. The polymerase of influenza A viruses plays a central role in the viral cycle, notably by driving the synthesis of viral messenger RNAs that are translated into viral proteins. Here we identify two human splicing factors, RED and SMU1, that associate with the viral polymerase. We show that these factors jointly regulate the splicing of the NS1 messenger RNA into the shorter NS2 messenger RNA, which encodes a key viral protein named NS2/NEP. We demonstrate that RED and SMU1 are required for efficient expression of NS2/NEP, and for the NS2/NEP-mediated intracellular trafficking of viral components. Overall, our results show that RED and SMU1 are essential for the replication of influenza A viruses. With respect to the need of novel anti-influenza therapies for epidemic and pandemic preparedness, the functional and physical interactions between these cellular splicing factors and the viral transcriptional machinery could be targeted to inhibit viral replication.


Vyšlo v časopise: Recruitment of RED-SMU1 Complex by Influenza A Virus RNA Polymerase to Control Viral mRNA Splicing. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004164
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004164

Souhrn

Influenza A viruses are major pathogens which pose continuous animal and public health challenges. Enhancing the knowledge of their life cycle, and especially the understanding of how viral components interact with the host cell, is essential to achieve better prevention and treatment of the disease. The polymerase of influenza A viruses plays a central role in the viral cycle, notably by driving the synthesis of viral messenger RNAs that are translated into viral proteins. Here we identify two human splicing factors, RED and SMU1, that associate with the viral polymerase. We show that these factors jointly regulate the splicing of the NS1 messenger RNA into the shorter NS2 messenger RNA, which encodes a key viral protein named NS2/NEP. We demonstrate that RED and SMU1 are required for efficient expression of NS2/NEP, and for the NS2/NEP-mediated intracellular trafficking of viral components. Overall, our results show that RED and SMU1 are essential for the replication of influenza A viruses. With respect to the need of novel anti-influenza therapies for epidemic and pandemic preparedness, the functional and physical interactions between these cellular splicing factors and the viral transcriptional machinery could be targeted to inhibit viral replication.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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