Every day, our body is locked in an incessant war against a perpetual onslaught of viruses. To defend against pathogens such as viruses, we have evolved a highly complex immune system with many lines of defense. These include our skin, which prevents pathogens from entering our body, our innate immune system, which attacks any foreign substances with an army of voracious phagocytes, and our adaptive immune system, which recognizes and specializes to counter the specific type of pathogen that is invading our body. However, if a virus manages to bypass all of that and enter our cell, then it is only a matter of time before it turns that cell into a viral cloning factory, producing countless more viruses to continue the viral onslaught. The only hope for the cell at this point is to signal nearby white blood cells to grant it a merciful death in the form of apoptosis before the virus takes complete control. Or is it? New research shows that the cell still has a fighting chance: a last line of defense called TRIM21.
TRIM21 at work:
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While the virus is still in our bloodstream, it is likely to have faced many antibodies, proteins that target pathogens by binding to specific surface molecules on the pathogen. In a recent experiment, researchers found that viruses often carry antibodies attached to its surface upon entering a host cell, and these antibodies can be used to destroy the virus from within its host. This is where TRIM21 comes in. The TRIM21 protein can attach itself to the virus by binding to the antibodies on the virus’s surface. At this point, TRIM21 calls upon a set of proteins called ubiquitin, which attach to TRIM21 and aggregate into a long chain. Normally, ubiquitin is used to tag cellular proteins for destruction so that their building blocks can be recycled and reused, and this is exactly what happens next. The ubiquitin chain attracts the proteasome, a giant protein degrading cellular recycling machine, to the virus. In an instant, the proteasome devours the entire complex of virus, ubiquitin, and antibodies, turning everything into shreds.
Aside from destroying the virus, TRIM21 also triggers various signaling pathways that eventually put the host cell and nearby cells on high alert and elicit inflammatory responses to bring more white blood cells to the area. Because the intracellular defense system shreds of viruses, it is very possible that some immune cells can use bits of the shredded viruses to alert our adaptive immune system and help our bodies “remember” this particular type of invader.
Ribbon diagram of TRIM21
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One benefit of this process is that TRIM21 only targets the antibody bound to the virus, and not the virus itself. Since antibodies can continually evolve to adapt to new pathogens within our lifetime, the TRIM21 mediated intracellular defense can target any strain of virus that enters the cell, given that our antibodies can recognize them. However, TRIM21 may not work against all viruses. Some viruses carry a viral envelope, a membrane similar in composition to our cell membranes, and usually shed them upon entering our cell, thereby losing any antibodies they carry with them.
Research on the TRIM21 protein have mainly been carried out on the Adenovirus
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For a long time, scientists have classed our immune system into either the innate or adaptive responses. Now, however, we have opened the door to a type of immune response that we never knew we had: the intracellular immune response. Undoubtedly, further research into this area will lead to new insights into our physiology, as well as unlock new treatments against deadly viral infections. Until then, we can only ponder what other secrets may lie on the other side of those tiny plasma membranes.