Researchers at Massachusetts General Hospital (MGH) are investigating a new way to block replication of hepatitis C virus “HCV” by targeting not the virus itself, but the genes that the virus exploits during its life cycle.

HCV has a high rate of replication that it can replicate a trillion particles per day. Also, due to its high rate of mutation, it can escape our immune system.

HCV replicates mainly within hepatocytes in liver by binding to receptors on the surface of the liver “CD81″ and human scavenger receptor class B1 “SR-BI”. Then it utilizes the intracellular machinery necessary for its replication. Upper right, virus particle enters cell followed by uncoating and release of positive-stranded HCV RNA genome. Viral genome is translated at the endoplasmic reticulum into the viral polypeptide (upper left). Viral replication complexes (red) are then assembled onto host-derived small membranous vesicles (yellow ovoids).

Transmission occurs by blood to blood contact, where it causes chronic liver infection in about 70-80% of patients & long term infections can cause liver failure or liver cancer.

HCV infection is usually treated with a six to eleven month regimen combining peginterferon and the antiviral drug ribavirin, but unfortunately, treatment is not successful in many patients and has serious side effects that some cannot tolerate.

Many drugs target viral enzymes, but due to the great ability of HCV to mutate, such approach lead to the emergence of resistant strains.

Recently, a new strategy has developed, which is to block human genes, which act as a cofactors for HCV infection. Using small interfering RNAs (siRNAs), researchers examined blocking of approximately 21,000 predicted messenger RNA transcripts in the human genome.

The siRNA scan found 96 genes that appear to have a role in viral replication, one gene codes for an enzyme called PI4KA, which is believed to be involved in the formation of membrane structures within the cell. Another group of genes contribute to formation of the coat.

So, by blocking these genes, HCV replication is stopped. At this time, these tested agents might not be suitable for therapeutic use.

Source & Image credits : Harvard Science.


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3 Responses to “Blocking genes who betrayed us!!!!”
  1. This new strategy involving siRNA seems promising, but I guess must be studied further in depth..since blocking a specific human gene say the one for PI4KA, would hinder the viral replication true, but wouldn’t it also affect the normal function of the basic human cell?? unless I guess, it had some sort of selectivity to the infected ones.
    Nice article.

  2. Hosam allam says:

    Me too, but I guess they can again use gene therapy as a replacement therapy to decrease side effects…
    So, let’s wait & see…

  3. rama saad says:

    That is a very nice interesting article. The field of gene therapy is evolving very powerfully offering radical solutions to many things, however i think the role of translational research’s role still has to be played so that we can know exactly how can we bring this to clinical application, for example in the case of HCV siRNA treatment, i totally agree with you and radwa that whether the inhibition of these genes would alter the normal genes’ function and if so, does this raise a question that we can optimize therapy by blocking certain genes and leave others or by blocking certain genes and concurrently using ribavirin. All of these questions are awaiting answers that are to be answered by translational research. Very nice article, thanks for share.

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