Season 4, Episode 3: Hep Burn & Melnikov
When Rachel and Wes visit the shelter where Rachel does volunteer work, they are shocked to learn that several of the regular shelter guests have died that night. It appears that many shelters across Toronto have been hit by an outbreak of a strange form of Hepatitis C. NorBAC investigates and finds evidence suggesting that Dr. Cove of the Toronto Division of Health deliberately targeted the city's intravenous drug users with a specially designed, fast-replicating Hepatitis C virus.
 Images provided courtesy of AXS Studio Inc and Shaftesbury Films. |
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Artist's rendition of 4 strains of HCV (A) and the recombined HCV "super strain" (B). |
IS IT POSSIBLE TO COMBINE FOUR STRAINS OF HEPATITIS VIRUS INTO ONE "SUPER-STRAIN" USING CELL CULTURES AND/OR MICE?
What is Hepatitis C?
Hepatitis is the collective name for a particular group of liver diseases. Hepatitis initially causes liver failure, in which the liver is no longer able to filter toxins from the blood. A typical hallmark of hepatitis is jaundice: the liver normally takes care of eliminating the brown-coloured waste product bilirubin to the digestive tract, but if the liver stops working the pigment can build up in eyes and skin, which then appear yellow. If Hepatitis is left untreated, the liver cells may eventually die. If that happens, only a liver transplant can prevent death, but most forms of hepatitis are treatable, or at least manageable.
The most common cause of hepatitis is infection with one of the Hepatitis viruses: A, B, or C. These three viruses are members of different virus families and infections with them are treated in different ways. The Hepatitis A virus is spread through eating contaminated food, but an infection with this virus often goes away by itself without treatment. Hepatitis B is often transmitted through sexual contact or by direct contact with infected blood, but can be cured with an antiviral drug. There are vaccinations available against both the Hepatitis A and B virus, but not against the Hepatitis C virus, which is also the most difficult to treat.
The Hepatitis C virus, or HCV, can only be transmitted by direct contact with infected blood. Blood transfusions with infected blood and shared needles are major sources of HCV infection. As many as 170 million people are infected with HCV world wide, of which about 240,000 are in Canada. There is no cure for HCV yet, but patients are treated with interferon to boost their immune system and with a general antiviral drug. Many people can survive with HCV for years on this treatment.
What is recombination?
There are six variations (genotypes) and several subtypes of the Hepatitis C virus, each of which has a slightly different genome. The different genotypes are found in different parts of the world: For example, types 1a and 1b are common in North America and Europe, while type 5 is almost exclusively found in South Africa.
In very rare cases, a person can get infected with two different genotypes of HCV from two separate infections. If these two viruses enter the same cells in the body, their genetic material can recombine. In the case of HCV, which uses RNA as its genetic material, recombination means that pieces of the RNA of one virus will connect to pieces from the other virus. Sometimes this new mix of genetic material is capable of producing a functional virus, and a new genotype - or strain - of the HCV virus is created.
 Image provided courtesy of Shaftesbury Films. |
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David explains how different strains of HCV can recombine in a person. |
Can viruses recombine in cell culture?
One way to study HCV- to understand how it infects people and how we can effectively treat such infections - is by growing human liver cells in culture dishes in a lab, and then infecting the cells with the virus. Producing viable HCV in cultured cells has only been possible for a few years, and only HCV genotype 2a has been successfully grown in culture. Because not all naturally occurring genotypes of the virus can grow in culture yet, it's not possible to get four virus types into the same cell and get spontaneous recombination.
What are humanized mice?
Another way to study HCV would be through the use of a humanized mouse model. A humanized mouse is a mouse that has been engineered to possess some human cells or tissues. They are often used to study new drugs for human diseases that mice can't catch or develop.
Depending on the specific human disease that the researchers want to study, they can use mice that have human cells in particular areas of interest for that disease. For example, some of the mice used in hepatitis research have human liver cells; these particular mice are used because their liver cells can be infected with the same virus that infects human livers. Regular mice can't be used in these studies, because the Hepatitis C virus does not infect mouse cells. Humanized mice have been used in HCV research to study hepatitis treatment methods, but have never been used to generate resistant viruses.
So?
It's currently not possible to grow and recombine four HCV viruses in cell culture. Only one of the genotypes has been successfully produced in cells in a culture dish.
But, if growing and manipulating hepatitis C viruses in culture becomes easier in the future, could Dr. Cove's scheme be carried out? Probably not. Experiments with mice and viruses are very strictly regulated and tightly controlled, so it's extremely unlikely that anyone - let alone a scientist in a municipal health lab - could get away with doing work like this, unnoticed.
DID YOU KNOW?
David tries to impress Meghan, a lab technician at the Toronto Division of Health, by mentioning his favourite virus: Mimi, the biggest virus known to man. The Mimivirus was first found in 1992 in a water tower in England, but was initially mistaken for a bacterium because of its size. It wasn't until 2003 that a group in France identified it as a virus and called it "Mimivirus" for "mimicking microbe". Not only is the Mimivirus very large in size for a virus, but also has a very large genome. With about a thousand genes, much more information is stored in the genome of the Mimivirus than in any other virus known to science!
-- Eva Amsen
Want to read and learn more?
Read what Health Canada has to say on hepatitis C:
www.hc-sc.gc.ca/iyh-vsv/diseases-maladies/hepc_e.html
Find out more about the use of cell culture in HCV research:
www.sciencedaily.com/releases/2007/01/070123092650.htm
Read about the use of a humanized mouse model in HCV research by clicking here:
www.natap.org/2008/HCV/022808_02.htm
To learn more about the Mimivirus, visit:
www.microbiologybytes.com/virology/Mimivirus.html
