Viruses are small intracellular parasites that invade the cells of virtually all known organisms. They reproduce by utilizing the cell's machinery to replicate viral proteins and genomic material, generally damaging or killing the host cell in the process; subsequentelly, a large number of newly generated viruses go on to infect other cells. Viruses are responsible for a wide variety of human diseases, ranging from the common (influenza and colds) to the exotic (AIDS, West Nile virus and Zika). Some viruses which are not dangerous to humans can also be exploited in technological applications, in addition, viruses find use in genetic engineering applications and increasingly in the design of new nanomaterials. At the very least, all viruses contain two components: the capsid (a protein shell), and a genome, consisting of either DNA or RNA. Some viruses also include accessory proteins to aid in infection, and in some cases a lipid bilayer to further protect their contents from the environment. The viral life cycle itself is deceivingly simple: viruses enter the cell, typically (but not always) through the interaction of their capsid with a receptor on the cell surface; the virus must then somehow disassemble its capsid to release its genetic material and any necessary helper proteins. The viral genome is then replicated and the proteins it codes for are synthesized to produce the raw material for the production of new viral particles; these new viruses then assemble and bud from the cell either through the membrane or upon cell death.
Spotlight: Anatomy of a Dormant Killer (Aug 2015)
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Retroviruses are parasites that pose a major health threat to humans (for example in case of HIV) and other animals (for example in case of RSV, M-PMV, MLV, and many more viruses). After a retrovirus hijacks a cell, the infected cell produces multiple copies of the virus which are then released into the host's bloodstream. These newly released viruses must mature before they can infect other cells. A strategy for preventing virus spread is therefore, to lock the viral particles in their immature, non-infectious state. However, to render the immature virus an attractive target for structure-based drug development one needs to know its chemical structure. Unfortunately, the complexity and size of the viral particle ― an incomplete hexagonal shell with a size close to 100 nm ― have prevented the experimental determination of the chemical, namely atomic level, structure of the virus. As reported recently, a team of computational and experimental researchers have provided an atomic structure of the immature retroviral lattice for the Rous Sarcoma Virus. The multi-domain RSV model was derived through a combination of state-of-the-art modeling techniques, including, cryo-EM-guided homology modeling, large-scale molecular dynamics simulations using enhanced sampling capabilities available in NAMD, together with experimental measurements such as X-ray crystallography and a wealth of biochemical data. Particularly, the model reveals novel features of the packing and dynamics of the immature capsid protein with implications for the maturation process and confirms the stabilizing roles of the so-called upstream and downstream domains of the immature RSV. More information is available on our retrovirus website, and in a highlight video.