'Tis the season, from Thanksgiving to New Year, when tens of millions of us will travel to see family and friends. As these trips draw near everyone will face the same dilemma -- what to pack? After laundry, ironing and folding, the next problem is which suitcase to choose; too small, too big, just right. What none of us think about during this time is the myriad of invisible virus particles that will be making the trip with us.
These nanoscale objects (a nanometer is one millionth of a millimeter, or 10,000 times smaller than the width of your hair) cling to our bodies looking for ways to get inside our cells and make new copies of themselves. During our trip, they will readily be exchanged with viruses taking trips with other people, either by transferring on surfaces or as aerosols in the air, especially if someone forgets to cover their face when they sneeze. Despite their apparently insidious size, and their potential for causing everything from the common cold to AIDS, viruses are not actively malign. They are in fact non-living collections of proteins and nucleic acids that simply fulfill Darwinian predictions about evolution. In their case they have evolved the property of infecting cells and replicating by using the host's molecular machinery to produce new virus particles that escape the cell looking for a new victim. Making their hosts ill, or even killing them, is just an unfortunate side effect of this process. It is, however, a side effect that results in devastating losses in crops, as well as being the cause of many serious illnesses and deaths in animals and people every year. Understanding these events in detail is a major goal of researchers who hope to find ways to deter these pesky hitchhikers.
Working with one group of viruses that contain RNA genomes, similar to those that cause the common cold or polio, Alex Borodavka, Roma Tuma and I have just made an interesting discovery about the ways that viruses pack for their trips. In the viral world the content of the suitcase is the nucleic acid that carries the instructions for making new viruses. The suitcase is made from viral coat protein molecules that clump together to form a protective shield for that nucleic acid. Just as we do when we get to our destinations, when viruses enter cells they unpack their nucleic acids from the protein shell and the process of making new virus particles can begin. The first stages of this process are making new copies of the nucleic acid instruction book and more coat proteins to make the newly required suitcases to pack them in. The RNA in our test viruses emerges from these events rather like our clothes do after a few days at our destination, crumpled in a heap and no longer neatly folded. At the end of our trips we may discover that our suitcase is a little too small after all because we have to work hard at getting everything to fit back in. Similarly new viral suitcases are pretty cramped, and something has to happen to fold their nucleic acid molecules neatly so that they will fit inside.
Using a spectroscopic technique that allows us to see viral particles one at time, we noticed the equivalent of a Harry Potter moment for virus assembly. When viral RNAs and viral proteins are mixed together the proteins leap onto the RNA and fold it up neatly. It is as if the suitcase and the contents pack themselves. Previously people assumed that the process was much more gradual than this. Interestingly, when viral coat proteins are given non-viral RNAs they leap onto those molecules too but are not able to fold them up. That means that the viral suitcases they try to build do not close properly and so their contents cannot survive the trip to a new host. These observations pose an interesting question.
Can we mess up a viral nucleic acid's travel plans by getting their coat proteins to treat them like non-viral equivalents? If we could we would have a powerful way to treat viral infections. Something to think about the next time you are stuck waiting for your plane, train or bus.
Happy Holidays!