MSGID: 1:317/3 64781f2b   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    How the flu virus hacks our cells    
    A team has discovered how the influenza A virus hijacks the mechanism for   
   importing iron into cells to invade its host    
      
     Date:   
         May 31, 2023   
     Source:   
         Universite' de Gene`ve   
     Summary:   
         Influenza epidemics, caused by influenza A or B viruses, result   
         in acute respiratory infection. They kill half a million people   
         worldwide every year. These viruses can also wreak havoc on animals,   
         as in the case of avian flu. A team has now identified how the   
         influenza A virus manages to penetrate cells to infect them. By   
         attaching itself to a receptor on the cell surface, it hijacks   
         the iron transport mechanism to start its infection cycle. By   
         blocking the receptor involved, the researchers were also able to   
         significantly reduce its ability to invade cells. These results   
         highlight a vulnerability that could be exploited to combat   
         the virus.   
      
      
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   FULL STORY   
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   Influenza epidemics, caused by influenza A or B viruses, result in   
   acute respiratory infection. They kill half a million people worldwide   
   every year.   
      
   These viruses can also wreak havoc on animals, as in the case of avian   
   flu. A team from the University of Geneva (UNIGE) has identified how the   
   influenza A virus manages to penetrate cells to infect them. By attaching   
   itself to a receptor on the cell surface, it hijacks the iron transport   
   mechanism to start its infection cycle. By blocking the receptor involved,   
   the researchers were also able to significantly reduce its ability to   
   invade cells. These results, published in the journal PNAS, highlight   
   a vulnerability that could be exploited to combat the virus.   
      
   Influenza viruses represent a major risk to human and animal health. Their   
   potential for mutation makes them particularly elusive. ''We already   
   knew that the influenza A virus binds to sugar structures on the cell   
   surface, then rolls along the cell surface until it finds a suitable   
   entry point into the host cell. However, we did not know which proteins   
   on the host cell surface marked this entry point, and how they favoured   
   the entry of the virus,'' explains Mirco Schmolke, Associate Professor in   
   the Department of Microbiology and Molecular Medicine and in the Geneva   
   Centre for Inflammation Research (GCIR) at the UNIGE Faculty of Medicine,   
   who led this work.   
      
   A receptor as a key to infection The scientists first identified cell   
   surface proteins present in the vicinity of the viral haemagglutinin,   
   the protein used by the influenza A virus to enter the cell. One of these   
   proteins stood out: transferrin receptor 1. This acts as a revolving   
   door transporting iron molecules into the cell, which are essential for   
   many physiological functions.   
      
   ''The influenza virus takes advantage of the continuous recycling of the   
   transferrin receptor 1 to enter the cell and infect it,'' explains Be'ryl   
   Mazel-Sanchez, a former post-doctoral researcher in Mirco Schmolke's   
   laboratory and first author of this work. ''To confirm our discovery,   
   we genetically engineered human lung cells to remove the transferrin   
   receptor 1, or on the contrary to overexpress it. By deleting it in   
   cells normally susceptible to infection, we prevented influenza A from   
   entering. Conversely, by overexpressing it in cells normally resistant   
   to infection, we made them easier to infect''.   
      
   Inhibiting this mechanism The research team then succeeded in reproducing   
   this mechanism by inhibiting the transferrinreceptor 1 using a chemical   
   molecule. ''We tested it successfully on human lung cells, on human lung   
   tissue samples and on mice with several viral strains,'' says Be'ryl   
   Mazel-Sanchez. ''In the presence of this inhibitor, the virus replicated   
   much less. However, in view of its potentially oncogenic characteristics,   
   this product cannot be used to treat humans.'' On the other hand,   
   anti-cancer therapies based on the inhibition of the transferrin receptor   
   are under development and could also be interesting in this context.   
      
   ''Our discovery was made possible thanks to the excellent collaboration   
   within the Faculty of Medicine as well as with the University Hospitals   
   of Geneva (HUG) and the Swiss Institute of Bioinformatics (SIB),'' the   
   authors add. In addition to the transferrin receptor 1, scientists have   
   identified some 30 other proteins whose role in the influenza A entry   
   process remains to be deciphered. It is indeed likely that the virus uses   
   a combination involving other receptors. ''Although we are still far   
   from a clinical application, blocking the transferrin receptor 1 could   
   become a promising strategy for treating influenza virus infections in   
   humans and potentially in animals."   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Influenza # Bird_Flu # Cold_and_Flu # Cancer   
             o Plants_&_Animals   
                   # Bird_Flu_Research # Virology # Molecular_Biology #   
                   Biology   
       * RELATED_TERMS   
             o Avian_flu o Flu_vaccine o Pandemic o Spanish_flu o   
             Influenza_pandemic o H5N1 o Gastroenteritis o Virus   
      
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   Story Source: Materials provided by Universite'_de_Gene`ve. Note:   
   Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Beryl Mazel-Sanchez, Chengyue Niu, Nathalia Williams, Michael   
      Bachmann,   
         He'le`na Choltus, Filo Silva, Ve'ronique Serre-Beinier, Wolfram   
         Karenovics, Justyna Iwaszkiewicz, Vincent Zoete, Laurent Kaiser,   
         Oliver Hartley, Bernhard Wehrle-Haller, Mirco Schmolke. Influenza   
         A virus exploits transferrin receptor recycling to enter host   
         cells. Proceedings of the National Academy of Sciences, 2023; 120   
         (21) DOI: 10.1073/ pnas.2214936120   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230531102006.htm   
      
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