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HCV virus replicated in laboratory

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  • Mark Middle Mountain
    http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=8400005 Scientists Replicate Hepatitis C Virus In Laboratory 02/22/05 -- For the first time,
    Message 1 of 1 , Feb 23, 2005

      Scientists Replicate Hepatitis C Virus In Laboratory

      02/22/05 -- For the first time, scientists have replicated hepatitis C virus
      (HCV) in the laboratory. The ability to replicate HCV in cell culture will
      allow researchers to better study the life cycle and biology of this virus
      and to test potential antiviral compounds, which may lead to new therapies
      for the liver disease that results from infection with HCV. Scientists at
      the National Institute of Diabetes and Digestive and Kidney Diseases
      (NIDDK), one of the National Institutes of Health (NIH), conducted the
      study, which appears in the Feb. 15, 2005 issue of Proceedings of the
      National Academy of Sciences (PNAS).

      "Until recently, research on this infectious disease has suffered from the
      lack of a robust in vitro model system," says T. Jake Liang, M.D., Chief of
      the Liver Diseases Branch of the NIDDK and co-author of the study. "Our
      model system produced viral particles that have all the properties of the
      whole virus. This evidence together with an analysis of the replicated viral
      RNA supports a conclusion of viral replication and production."

      The NIDDK group used a strain of HCV that would have applications to the
      greatest number of people - genotype 1, the major type of HCV of human
      infections worldwide and the type most resistant to current therapies. They
      constructed an HCV replica using a DNA copy of the original HCV
      single-strand RNA genome. They placed the DNA copy between two ribozymes,
      RNA molecules that have enzymatic function and can cleave RNA sequence at
      specific locations. These two ribozymes were designed to generate the
      correct ends of the HCV genome and to act as start and stop buttons to gene
      activity. The construct was "naked," meaning that it contained only nucleic
      acids, the genetic material of the virus, and did not have the HCV viral
      envelope, a protective shell of lipids and proteins that surrounds the viral
      RNA in fully-formed HCV. The naked HCV construct was then placed into human
      liver cells in a cell culture medium.

      The NIDDK scientists found evidence of HCV proteins and HCV RNA within the
      human liver cells in the culture. Electron microscopy showed evidence of
      high levels of viral particles resembling fully-formed HCV outside of the
      human liver cells in the culture medium. The researchers believe that the
      HCV construct contained within the human liver cells behaved like a true HCV
      infection by producing fully formed copies of the virus and releasing them
      from the host cell into the culture medium. Further testing is needed before
      the researchers can determine if the viral particles produced in this system
      are in fact infectious. Also, this system only represents the tail end of
      the viral life cycle - viral replication, assembly and release from host
      cells. Another HCV model system is needed to show the beginning stages of
      the viral life cycle - viral entry into host cells and viral activity in the
      host cell before replication.

      "With this cell-based system, we can screen compounds with a cell-based
      assay to look for inhibitors of virus replication," says Liang. "We can also
      apply this technique to develop model systems for other similar viruses."

      HCV is a small, enveloped, single-stranded RNA virus in the family
      Flaviviridae. HCV is a major cause of liver disease in the United States and
      the world. One in a series of hepatitis viruses, HCV accounts for about 15
      percent of acute hepatitis cases, 60 to 70 percent of chronic hepatitis
      cases, and up to 50 percent of cases of cirrhosis, end-stage liver disease,
      and liver cancer. Almost 4 million Americans, or 1.8 percent of the U.S.
      population, have antibodies to HCV indicating ongoing or previous infection
      with the virus. Approximately 10,000 to 12,000 deaths each year in the
      United States are due to HCV.

      Source: NIH/National Institute of Diabetes and Digestive and Kidney Diseases

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