2nd paper

Kate Sakmann
03/24/08
Interferons and Hepatitis C
Hepatitis C was found in close to 200,000 individuals world-wide during the 1980s, most of which reside in developing countries. But now, thanks to recent medical developments and more advanced technology, the number of new cases per year has deteriorated to roughly 20,000 infected individuals. Scientists in the UK and India are working on creating a less-expensive drug that would halt the replication of the hepatitis C virus. This drug includes a unique molecular machine called alpha-2 interferon. This new drug, which is scheduled for release within the next three years, would especially aid the population of India. Compared to industrialized countries, developing countries, such as regions of Africa, the Western-Pacific, and South-East Asia, experience a much greater struggle with the prevalence of the hepatitis C virus. To aid in this struggle, the interferon is being used as the basis of modern treatment for the hepatitis C virus. Not only is interferon a chemical messenger that promotes a series of immune responses, but it can also interrupt the growth and multiplication of a viral infection.
Hepatitis C is a disease that affects the liver, resulting in liver inflammation. It is a blood-borne infection, so it is transferred between individuals whose blood comes in contact. The viral molecule consists of RNA that is enclosed within the core of the virus with a surrounding envelope containing attached proteins. The RNA is transcribed to DNA, which is divided into sequences of nucleic acids that code for each component of the virus. For example, one part of the DNA codes for the core of the hepatitis C virus and another part codes for the envelope. In this way, the virus can quickly replicate and travel through the bloodstream.
To prevent the spread of viruses and bacteria, immune cells produce the protein alpha-2 interferon, which consequently plays a significant role in the process of hepatitis C pathology. Figure 1 shows an image of the basic structure of an interferon, a cytokine molecule that has two main functions in eliciting immune system responses. First, when a virus such as hepatitis C attacks cells, interferon reacts by signaling other cells which in turn causes these other cells to launch their own immune mechanisms. Second, interferon can also correspond with immune cells that can kill the infectious pathogen, which in the case of hepatitis C is a virus.
There are three types of interferons in humans: alpha, beta, and gamma. Interferon gamma is produced by activated T-cells and interferons alpha and beta can be produced by a variety of cells, which include T-cells and B-cells. T-cells and B-cells fight infections as major components in the immune system’s response to invading pathenogenic material. Interferons are within a subfamily of the cytokines. Cytokines are molecules—proteins and peptides—used as a form of chemical communication between cells. Pathogen surface molecules attach to macrophage surface receptors and the macrophage then ingests the bacteria. Immediately, the macrophage releases cytokines, which travel to other cells, delivering their messages via cell-surface cytokine receptors.
Figure 1: Basic interferon structure [2].
The left-hand picture in Figure 1 shows the basic components of the cytokine protein interferon. The components of the interferon cause it to be classified as a molecular machine because of its intricate structure and function. Interferons are a part of the four alpha-helix bundle family of cytokines. They are composed of four alpha-helices (shown in red in Figure 2), which bind DNA through the structural motif of helix-turn-helix. This motif contains two alpha-helices, which resemble springs, with a short amino acid link; this motif is also found in many proteins and is thought to regulate gene expression. DNA and protein interactions are regulated by one alpha-helix, while the other helix functions as a means of recognizing the correct DNA. The helix that recognizes the DNA constitutes the C-terminal, or the amino acid end of the motif that has a free carboxyl group attached; the helix that regulates DNA and protein interactions constitutes the N-terminal, or the amino acid end of the motif that has a free amine group attached. The C-terminal and N-terminal are shown as the yellow, white, and blue balls attached at the end of the helices in Figure 2.
Interferon is triggered as a response to a virus invading the cells in the body. Once one cell in the body is infected with a virus such as hepatitis C, the gene that codes for the protein interferon is activated. This way, all of the surrounding cells that have yet to be infected can prepare for when the initially infected cell bursts and releases thousands of the now replicated virus. These interferons are incredibly important in the fight against invading RNA viruses. When unusually large amounts of double stranded RNA molecules are present in a cell, the gene that codes for interferon production is activated and interferons are secreted and sent to surrounding cells. The cells that receive the interferon are warned of the pending invasion and thus begin producing protein kinase R. This protein is activated when the virus enters a cell that has been warned by the interferons. It then phosphorylates the protein elF-2. Once phosphorylated, this protein can no longer efficiently produce the proteins that the mRNA strand codes for, or in other words, its ability to initiate translation is diminished. Ribosomes can no longer effectively function because the virus replication process was interrupted. Because of this immune system response, the host cell and its inhabitant virus are killed. This defeat of the virus is the ideal result being searched for be a company called PolyTherics.
PolyTherics is in the process of developing a technology that would produce a homogenous material through a controlled reaction. This process would ultimately result in a much for efficient and cost-effective drug [1]. This drug would contain a pegylated interferon, which is represented in both Figure 1 and Figure 2. Alpha-2 interferon is used, and a polymer (polyethylene glycol, or PEG) is attached to the protein to make it useful within the human body, otherwise it would be rapidly destroyed. PEG is shown as the orange blob of molecules on the left side of Figure 2 and as yellow and blue strands wrapped around the interferon in Figure 1.. Because the polymer PEG is attached to the interferon, the structure is then referred to as a PEGylated interferon. Although this process of attaching a polymer to a protein is not new, the technology used to produce it and make it less-expensive is.
Figure 2: PEGylated interferon [1].
The new drug currently being researched and developed by PolyTherics, the company consisting of scientists in the UK and India, will greatly aid those living in the developing world. These impoverished people will be able to afford a cure for a wide-spread and problematic disease. Also, if the poverty-stricken cannot afford the drug even at its reduced price, it will be easier for industrialized countries to help because, since the price is reduced, their monetary donations will go a lot further by supplying a greater amount of medicine for the same price. Another way the industrialized world can aid developing countries suffering from the hepatitis C virus is by donating supplies, such as needles to medical centers that are based in the developing world, since the sharing of needles is the most common route of transmission for the virus. Therefore, further research on the protein interferon and its role in hepatitis C treatment, and the production of drugs containing interferon will significantly aid those infected by hepatitis C. This is due not only to the remarkable immune responses triggered by interferon, but also to the protein’s ability to simultaneously interfere with the growth and multiplication of the virus.

Works Cited
[1] Gill, Victoria. "PEG-Ing Makes Cheaper Drugs for Developing Countries." Royal Society of Chemistry. Feb. 2007. Royal Society of Chemistry. 3 Mar. 2008 .
[2] "Pegasys Improves Things for Patients with Chronic Hepatitis C." Roche [Healthcare Innovation Website]. 21 Jan. 2008. F. Hoffmann-La Roche Ltd. 3 Mar. 2008 .
Bibliography
"World Health Organization: Worldwide Statistics for HCV." HCV Advocate. 2008. Hepatitis C Support Project. 3 Mar. 2008 .
"Understanding Interferon." ImmunityFacts.Com. Center for Immune Research. 3 Mar. 2008 .