One of the reasons I tend to stick to physics is that the subject is quite simple. Any part of chemistry is more complicated than all physics as a whole. Biology, in all its wonders, simply stuns how little I have left of mind.
With that in mind, the idea of me writing about viruses seems like a joke. But a great development that allows researchers to track individual viral particles and see them invade their unfortunate victims is simply too good to pass up.
Did the bright virus illuminate the well used path?
Tracking individual virus particles is not exactly new. The idea is to attach some type of molecule that shines to the virus. Then, you hit the sample with an exciting laser and look for bright points of light. Optical microscopes can track the location of the virus with very high accuracy.
With this type of technology, you can learn a lot about how viruses move. And if you make specific parts of the cell glow a different color, you can see how often the virus interacts with those parts (for example, a specific cell surface receptor) based on how often the two bright spots merge in one.
One of the disadvantages is the bright molecule in the virus, which is usually attached to the outer layer. In this case, the molecule can interfere with the normal activity of the virus. The virus can be prevented from entering a cell because the bolt cutter that it normally uses is blocked by the large bright molecule that attached it. Instead, it would be preferable to place the slightly shiny virus inside, where (hopefully) the behavior does not change.
A group of researchers from China has done exactly that. But this seems to be one of these heroic experiments that only works when the wind blows from the right side.
The researchers replaced the bright molecule with a quantum dot. A quantum dot is a small drop of material that, by virtue of its small size, will shine when the light excites it. Even better, the brightness color is adjusted by changing the size of the drop, so that we can make almost any quantum dot color we want.
To obtain the quantum point within a virus, the researchers made use of the procedure by which a virus replicates. A virus breaks into the outer membrane of a cell and, once inside the outer defenses, reaches the inner ring of the defenses (the membrane that surrounds the nucleus). After persistent siege work, some viruses enter the cell nucleus where they can really get to work. These viruses hijack the cell’s replication machinery to produce copies of its own DNA, while forcing the cell’s protein production hardware to build new capsules. The cell, like a kind of sorcerer’s apprentice spell that went wrong, does this until it opens suddenly, spraying contagion everywhere.
The researchers interfered with this process by attaching a single-stranded DNA to the quantum point and, by various nefarious means, convinced the cell that the quantum dots belonged to the cell nucleus. To ensure that the virus absorbed the point, they used CRISPR / Cas9 to edit a small stretch of DNA in the viral genome. The replacement DNA was complementary to the chain attached to the quantum point, allowing them to form base pairs. Then, during replication, the quantum point could be incorporated into the virus’s DNA. After which, the DNA, along with the quantum dot, was packaged in the virus and expelled from the cell.
Of course, not all virus particles contain a quantum dot, because the process of incorporation is governed by the random possibility that you will encounter what else inside the nucleus. However, the researchers managed to get enough virus labeled to perform some fun experiments.
Lighting a new light on old results
Because this is a new labeling technique, the researchers did not study anything particularly novel, but showed that they could confirm results that were already known. They showed films of viral particles that enter the cells and shoot along the cell’s microtubule network as if they were in a subway system. The researchers could also see the virus entering the nucleus as well. The films of his observations are available here.
Will everyone be eager to use this new labeling technique? Well, maybe not. First, this only works on viruses that have DNA, rather than RNA, which eliminates the consideration of a fairly old type of virus. Second, the procedure is not simple. The document is almost completely dominated by confirming that each step of the process (and there are many of them) really worked as planned. For me, this suggests that it would take a competent researcher a lot of time to replicate this work, much less start using it for his own research purposes.
Nano Letters, 2020, DOI: 10.1021 / acs.nanolett.9b05103 (About DOI)