We find a new way that viruses hijack cells
Veronique Greenwood reports in Quanta:
ruses travel light. Most carry just their genetic material and a few tools to break into the cells of their hosts — after that, they hijack the host’s own machinery to manufacture thousands of copies of themselves. In recent decades, biologists have gained a clearer picture of just how this heist is pulled off. Many viruses, it turns out, suppress the messages that cells send to control their daily operations. This information interference shuts down some cellular functions that the attacking virus doesn’t need, and boosts others.
But some viruses do something more subtle and complex, as biologists at the University of California, San Diego, reported recently. The scientists looked at cells infected with cytomegalovirus, a common cause of birth defects. CMV infection doesn’t block cellular messages; instead, it changes their content, the team found. In a new paper in Nature Structural and Molecular Biology, they detail thousands of changes in these host communications, which may be the virus whispering sedition to remodel the cell.
To understand the importance of what is going on here, first consider how the cell functions normally. At the heart of the whole affair is the DNA — a sort of code book of instructions for how to make everything in the cell — which is kept under lock and key in the nucleus. When the cell needs to manufacture a protein, the relevant portion of the DNA is transcribed. That transcript, called a messenger RNA, leaves the nucleus and heads to the machinery that will use it as a template to make the new protein.
But along the way, the RNA can be edited in a number of ways. It might acquire tags that give extra instructions on how to handle it; it might have parts snipped out; it might gain or lose end pieces that make it easier or harder to use. In the normal way of things, the cell employs all of these strategies to control its own functions. In fact, the altering of these RNA messages, so different versions of proteins are made at different times, is key to the process of development. The same gene can be used to make one version of a protein in a human fetus and a different version in an adult.
But as with so many things, once those tools are under the control of an enemy, it’s a different story. A virus that can edit a host’s RNA messages would be able to create versions of proteins that favor a virus’s goals, without ever having to break into the nucleus. And because CMV is known to be somewhat peculiar — it is one of those viruses that don’t suppress hosts’ messages the way many others do — the UCSD group, led by Gene Yeo, a molecular biologist, and Deborah Spector, a virologist, decided to see if it was doing something else to the host’s RNA.
First, the team infected human cells with CMV. Then they extracted the RNA made by the cells at different time points over the course of the infection. The extractions revealed the sum of the chatter between the nucleus and the protein-making machinery. They looked to see how many edits — extra tags, altered end pieces and so on — there were, as compared with healthy, control cells. And while the early stages of infection didn’t show dramatic differences, the late stages, when the infected cells were gearing up to burst and release tons of new viruses, were a different story.
These cells showed more than 2,500 alterations that did not appear in controls, a number that surprised Ron Batra, the UCSD researcher who is first author on the paper and has studied diseases that involve RNA changes. While it isn’t surprising that a virus makes such changes — after all, the goal is to take over the cell, and virologists have known about individual instances of these alterations for some time — the number of edits was striking. That’s as many changes from normal as might be seen in some cancers or ALS, he said. . .
Things are more complex than one might assume. Evolution has had a lot of time to try variations.