Dangers In and Out delivers its genome by ejection/injection (rather than by disassembly of its capsid). Most of these pressurized viruses are likely to be bacteriophages, which generally do not enter their host cell but rather inject their genome upon binding to the outer cell membrane (see the figure, panel A). The genome involved must be dsDNA, because singlestranded nucleic acid is easily compressible and hence does not get sufficiently pressurized upon being confined. It is thus no coincidence that most bacterial viruses have dsDNA genomes. In contrast, plant and animal viruses, whose capsids generally enter the cytoplasm of their host cells and then disassemble, mostly have ssRNA genomes. On the other hand, a mammalian dsDNA virus such as herpes, whose capsid enters the cytoplasm of its host cell by passing through the outer cell membrane, must still inject its genome into the nucleus upon binding to a nuclear pore complex (see the figure, panel B). The pressure in its capsid should be comparable to those in bacteriophages. The motor protein that packages its genome is thus expected to exert forces as high as tens of piconewtons. In many phage life cycles, the freshly replicated, not-yet-packaged DNA genomes are linked together in a polymer. High-resolution cryoelectron microscopy studies on phage P22 (11) have revealed the configuration of the packaged DNA and shown how the motor protein complex acts as a pressure sensor when a certain density of DNA is achieved. At this point, packaging stops and the DNA is cut. As always, new understanding raises new questions. For example, because the host cell cytoplasm has an osmotic pressure of several atmospheres, phage ejection stops when the capsid pressure drops to a few atmospheres; what drives delivery of the rest of the genome? In some cases, it is transcription of the genes that have already been delivered; in others, it may involve the influx of water through the phage to accommodate the growth of the host bacterium (12).

State-of-the-art biophysical studies will help to elucidate these and other issues, such as how capsids can withstand pressures on the order of 50 atmospheres. Notable among these studies are the reconstitution of bacteriophage λ “from scratch”(13), the probing of elastic properties of individual viruses by atomic force microscopy (14), the observation of genome ejection from single viruses by fluorescence microscopy (15), and the simulation of protein capsid assembly, as well as single-