Season 4, Episode 5: Suspicious Minds

The NorBAC team looks into an alleged poisoning of a politician's daughter in Ottawa, only to find out that her symptoms were caused by a thyroid nodule. They also attempt to treat a woman in Nebraska who has vaccinia, a smallpox-like disease. She receives a drug that hasn't yet been tested in humans; unfortunately, the treatment could not save her, perhaps because her disease had already progressed too far for it to work. Meanwhile, the engineered red blood cells that Rachel gave Wes reduced the amount of Hepatitis C virus in his body, despite first giving him an allergic reaction. After this treatment, Wes leaves for Sweden to participate in a trial study to try to get rid of the Hepatitis virus completely.

IS IT POSSIBLE TO TRAP THE HEPATITIS C VIRUS WITH ENGINEERED RED BLOOD CELLS?

What happens when the Hepatitis C virus infects a cell?

Viruses like the Hepatitis C virus, or HCV, can't replicate by themselves. They use proteins from the organism they infect to copy and process their genetic material to produce viral proteins. But first, they must enter the cells of the host organism.

Image provided courtesy of AXS Studio Inc and Shaftesbury Films.

HCV infecting a liver cell.

To enter a cell, a virus starts by attaching to certain receptors on the outside of the cell. Different viruses are recognized by different receptors, and in the case of HCV there are several receptors needed to recognize and take up the virus.

What is the CD81 receptor?

One of the receptors that HCV binds to is called the CD81 receptor. This receptor is present on most human cell types, but not on red blood cells. The red blood cells that Rachel got from a lab in Amsterdam had been genetically engineered in such a way that they do have the CD81 receptor.

If CD81 was the only receptor that HCV needed to enter a cell, then red blood cells with CD81 would be able to take up HCV. However, several studies suggest that CD81 doesn't act alone; rather, a combination of receptors is needed to pull the HCV virus into the cell. The engineered red blood cells would need to have all the necessary receptors to be able to take up HCV.

Can red blood cells trap a virus?

When mammalian red blood cells develop, they lose their nucleus. The nucleus of a cell contains the DNA as well as the machinery needed to copy DNA, transcribe it to RNA, and process the RNA. It's this type of machinery that a virus needs to "hijack" in the host organism to be able to copy the virus' genetic information and make viral proteins. If a virus should end up in a red blood cell, it wouldn't be able to replicate itself or infect other cells after that. In essence, it would be "trapped".

This method hasn't been studied yet for Hepatitis C, but red blood cells have been engineered with a receptor called CAR, which is specific for Coxsackie B virus. These engineered red blood cells were successfully used in mice to trap the virus, and reduced the levels of virus in the blood. Not all the virus was trapped, though, so the mice were still infected. Other researchers are trying to develop this method to make red blood cells that specifically trap the human immunodeficiency virus (HIV).

If a virus has already multiplied and is spread out through the whole body of its host, it's unlikely that these traps can catch all of it. Nonetheless, researchers hope that even reducing the viral load might give the immune system a chance to fight off the rest of the virus.

So?

Red blood cells can be modified to have a cell-surface receptor that recognizes a certain virus, and the cells can then take up that virus and stop it from replicating any further. However, this has not yet been done for the Hepatitis C virus. Hepatitis C needs more than one receptor to enter a cell, and the exact mechanism by which it's taken up is still being investigated. Once this is clearly understood, it might be possible to genetically engineer red blood cells in such a way that they can trap HCV. But these cells would not be able to trap all of the HCV, because there are still other cells in the body that the virus can enter in order to replicate. The best that engineered red bloods cells can do is to reduce the amount of virus in the body.

Image provided courtesy of Shaftesbury Films.

Wes in the hospital, thinking about what lies ahead.

Notice that in this episode Wes doesn't completely recover: the viral load of HCV is reduced, but he is still going to receive further treatment to try and completely get rid of the virus altogether. If HCV-trapping red blood cells were a reality, reducing the viral load is indeed probably the best it can do.

DID YOU KNOW?

In investigating the presumed poisoning of an Ottawa city counselor's daughter, the NorBAC team considers cholinesterase inhibitors from pesticides or nerve gas as a possible cause. Cholinesterase inhibitors are chemicals that, as the name suggests, inhibit the enzyme cholinesterase. Cholinesterase breaks down a chemical in the nervous system called acetylcholine, which acts as a neurotransmitter, or chemical that carries signals from the brain to the rest of the body. When cholinesterase is inhibited, the neurons that respond to acetylcholine keep on signaling, which can cause muscle spasms and paralysis.

Some snake venoms contain cholinesterase inhibitors that paralyze their victims. Through this same mechanism, cholinesterase inhibitors can kill insects as well, which is why they are used in pesticides. The nerve gas sarin, discussed in the fact sheet for episode 9 of the first season also works by inhibiting cholinesterase. However, low doses of cholinesterase inhibitors are also used as medication against Alzheimer's disease when there is not enough acetylcholine signaling.

-- Eva Amsen

Want to read and learn more?

To read about CD81 and other receptors needed for HCV entry into cells, visit:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez& artid=1087871

Find out how red blood cells can be engineered to trap a virus:
http://www.nytimes.com/2007/03/27/science/27viral.html

To learn about cholinesterase and its inhibitors, visit the Protein Data Bank:
http://www.rcsb.org/pdb/home/home.do