Today I will review an article that I really enjoyed reading. However, before we get to the article, I want to give you the backstory to how I came to read it. It started on a regular lab day. One of my friends posted a news article on Google Buzz that discussed this paper. Of course, the news article heralded this paper as ushering in a cure for the common cold in a matter of a decade. This was intriguing enough (and so difficult to believe) that I decided to read the article and formulate my own opinion. After reading the article, I was thoroughly impressed by the science and the findings in the paper, and thoroughly disappointed in how over-hyped the news article was. In my disappointment (and in my quest to generate even more followers), I tried to find a way to write about this article in a way that is 1.) Honest, 2.) Exciting, and 3.) Easy to follow. The following is the final product of my labors. I'll let you judge it.
The paper I'll be discussing, Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21), is currently free to read, so if you don't have access to PNAS through a university, you can still read it! How awesome is that! Anyway, in this paper, Mallery, McEwan, and Bidgood (three first authors) discuss a protein, TRIM21 and its role in immunity. Now, before we can get into the details of the paper, we need a quick reminder of how our immune system works. The immune system responds to pathogens (disease-causing organisms) in two ways. First, there is a general recruitment of immune cells to the site of cellular damage. This process is why your finger turns red when you poke it with a pin. The second half of the immune system is what confers immunity and prevents you from catching the same disease twice (a la chicken pox). This system uses proteins called antibodies. Each antibody is designed to recognize a particular part of a pathogen and will bind to it, signaling for other immune cells to come and destroy the pathogen.
Viruses (which cause AIDS, the cold, the flu, hepatitis, and many other diseases) are pathogens that must enter a human cell and incorporate their genetic material into the cell. In doing this, they hijack the cell and force it to make copies of the virus, which then go on to infect other cells and other people. It was thought that, once a virus entered a cell, that the cell was pretty much a lost cause and should be killed by immune cells, sacrificing one cell for the good of the body. However, this paper changes this line of thought completely. For those of you not in science, this is a HUGE shift in thinking, and may very well be Nobel-prize-worthy.
Anyway, let's discuss this paper and its paradigm shifting discovery. The researchers here showed that TRIM21 is a protein that, when expressed in cells at high enough levels, will prevent the spread of virus in cells in a dish, if the viruses are coated first with antibodies. There are no immune cells present in this experiment, meaning that the eradication of the virus is being accomplished by plain, ordinary cells. The researchers then go on to prove that TRIM21 binds to the constant part of the human antibody (meaning that it recognizes ALL host antibodies).
What happens from here is a little less clear, though very exciting. TRIM21 is an E3 ubiquitin ligase. Ubiquitin ligases attach the protein ubiquitin to themselves or other proteins as a way to send the protein to the proteasome (where the protein is destroyed). NOTE: This is a very simplified and slightly inaccurate description, but it will suffice for the topic of this article. It looks like TRIM21 ubiquitinates itself, targeting itself to the proteasome. Because it is attached to the antibody which is attached to the virus, these both get dragged into the proteasome. Thus TRIM21 is now the protein equivalent of a kamikaze pilot. While the evidence for this is not strong enough to be confident that this is really how it works, the available evidence points in this direction.
All in all, this is an interesting paper with great science. However, the assumption that this will quickly lead to a cure for the cold is somewhat misguided. Antibody recognition of the virus is critical for the success of TRIM21-mediated viral destruction. The cold virus is tricky, though, as it mutates frequently, making it difficult for antibodies to keep up with the virus. Still, the discovery is intriguing and changes our view of how immunity works.
All right. Stay tuned for more posts! Your homework is to post the popular-culture equivalent to TRIM21 (from film, literature, tv, video games, etc.) I'm looking forward to your answers!
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