Viral attachment made easy
The first step in viral infection is the attachment of the virus to whatever cell it is going to take over. Since viruses are essentially inert particles when outside of a host cell, the attachment of the virus occurs via random diffusion of the viral particle until it happens to hit an appropriate target. More virus particles, or more potential hosts, will maximize the likelihood that a favorable interaction leading to viral replication might occur. Seeing this process occur in real time is impossible, as viruses are too small to be visualized by the light microscope, which is the only technique that we have to observe living cells.
Via io9, and reporting a new study in the journal Science, comes a description of the events which lead up to a specific virus called a phage taking over a bacterial cell by inserting the virus DNA into the host. The study takes advantage of a microscopic technique called cryoelectron microscopy. Standard electron microscopy offers several orders of magnitude improvement in magnification and resolution over the light microscope, allowing us to see viruses. Unfortunately, techniques to prepare specimens for observation using electron microscopy are harsh, and to some extent can distort biological structures. Cryoelectron microscopy freezes specimens extremely rapidly using liquid nitrogen, and can eliminate the need for the preparation chemicals.
Using cryoelectron microscopy (CEM), researchers at the University of Texas Medical School examined the interaction between a bacterial virus called T7 and a bacterial minicell. Viruses and minicells were snap frozen at different points in the attachment process, and visualized by CEM to obtain “snapshots” of the interaction process. By looking at the snapshots, the researchers were able to develop a new model of the attachment process for viruses to their host. Bacteriophages typically have tail fibers that interact with proteins on the host cell surface, and initiate the attachment process. This study showed that the tail fibers, instead of extending out away from the phage, are actually bound up around the phage head, or capsid. The virus particle moves randomly, and if it contacts an appropriate target, the tail fiber on that side of the capsid binds to the target. The rest of the tail fibers then will rotate to secure the attachment of the virus to the host. Full attachment leads to a change in conformation of the virus, and penetration of the host membrane to insert the virus DNA. It is critical to keep in mind that at no time do any of these steps represent an active process on the part of the virus; binding of the virus is a completely random event, and when it occurs, the proteins in the virus shift conformation to insert the virus DNA into the target cell.
Snapshots in this process were collected, and used to make a video animation of the process, which I think is the coolest thing I’ve seen on the Internet this week:
It is likely critical that the tail fibers undergo a shift in conformation as seen in the video, as movement of the fibers to the new position is what enables the movement of the central sheathe to penetrate the bacterial cell, and enable the virus DNA to be inserted.