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   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Hep C: Mystery of how deadly virus hides in humans is solved    
      
     Date:   
         July 5, 2023   
     Source:   
         University of Copenhagen - Faculty of Science   
     Summary:   
         With a new method for examining virus samples researchers have   
         solved an old riddle about how Hepatitis C virus avoids the human   
         body's immune defenses. The result may have an impact on how we   
         track and treat viral diseases in general.   
      
      
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   With a new method for examining virus samples researchers from the   
   University of Copenhagen have solved an old riddle about how Hepatitis   
   C virus avoids the human body's immune defenses. The result may have an   
   impact on how we track and treat viral diseases in general.   
      
   An estimated 50 million people worldwide are infected with with chronic   
   hepatitis C. The hepatitis C virus can cause inflammation and scarring of   
   the liver, and in the worst case, liver cancer. Hepatitis C was discovered   
   in 1989 and is one of the most studied viruses on the planet. Yet for   
   decades, how it manages to evade the human immune system and spread   
   through the body has been a riddle -- one that Danish researchers have   
   become the first to solve.   
      
   A new method for examining virus samples has led researchers at the   
   University of Copenhagen and Hvidovre Hospital to the answer, which is:   
   the virus just puts on a 'mask'.   
      
   By donning a mask, the virus can remain hidden while making copies of   
   itself to infect new cells. The mask cloaks the virus in the form of a   
   molecule already in our cells. Disguised by the molecule, our immune   
   systems confuse the virus with something harmless that needn't be   
   reacted to.   
      
   "How the Hepatitis C virus manages to hide in our liver cells   
   without being detected by the immune system has always been a bit of a   
   mystery. Our revelation of the virus' masking strategy is important, as   
   it could pave the way for new ways of treating viral infections. And it   
   is likely that other types of viruses use the same trick," says Associate   
   Professor Jeppe Vinther of the Department of Biology, who together with   
   associate professor Troels Scheel and professor Jens Bukh from Copenhagen   
   Hepatitis C Program headed the research.   
      
   Camouflage for a malicious virus The mask used by the hepatitis virus to   
   hide in our cells is called FAD, a molecule composed of Vitamin B2 and   
   the energy carrying molecule ATP. FAD is vital for our cells to convert   
   energy. The FAD molecule's importance and familiarity to our cells makes   
   it ideal camouflage for a malicious virus.   
      
   For several years, the research team had a good idea that FAD was helping   
   the virus hide in infected cells, but they lacked a clear way to prove   
   it. To solve the challenge, they turned to Arabidopsis, a well-known   
   experimental plant among researchers.   
      
   "We were getting desperate to find a way to prove our hypothesis, which   
   is when we purified an enzyme from the Arabidopsis plant that can split   
   the FAD molecule in two," explains Anna Sherwood from Department of   
   Biology, who together with Lizandro Rene Rivera Rangel are first authors   
   of the study.   
      
   Using the enzyme, the researchers were able to split the FAD and prove   
   that the hepatitis C virus used it as a mask.   
      
   Other viruses probably use the same trick Like both the coronavirus   
   and influenza virus, Hepatitis C is an RNA virus. Its genetic material   
   consists of RNA that must be copied once the virus enters its host   
   organism. New RNA copies are used to take over new cells, and one end   
   of the RNA's genetic material is masked by the FAD.   
      
   According to Jeppe Vinther, it is very realistic that other RNA viruses   
   use similar masking techniques to spread without being detected by   
   cellular control systems. In fact, researchers have already found another   
   virus that uses the same strategy. And there are likely more.   
      
   "All RNA viruses have the same need to hide from the immune system and   
   there is a good chance that this is just the beginning. Now that we're   
   attuned to this trick, it opens up the possibility of developing new   
   and perhaps improved methods of tracking and treating viral infections   
   in the future," concludes Jeppe Vinther.   
      
   The research is funded by Independent Research Fund Denmark, as well   
   as several other Danish and European foundations and conducted in a   
   collaboration between Jeppe Vinther's research group at the Department   
   of Biology, University of Copenhagen, and Troels Scheel and Jens Bukh's   
   research groups from the Copenhagen Hepatitis C Program, which are located   
   at UCPH's Department of Immunology and Microbiology and the Department   
   of Infectious Diseases at Hvidovre Hospital.   
      
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   Journal Reference:   
      1. Sherwood, A.V., Rivera-Rangel, L.R., Ryberg, L.A. et al. Hepatitis C   
         virus RNA is 5'-capped with flavin adenine dinucleotide. Nature,   
         2023 DOI: 10.1038/s41586-023-06301-3   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230705115127.htm   
      
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