Viruses
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: Atomic Resolution HIV Capsid Pays Off (Apr 2016)
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When experimental-computational biologists embarked on the great challenge of resolving the atomic level structure of the HIV virus capsid that contains the virus' deadly genetic cargo, they were advised by referees not to try as the capsid is too big, too irregular, and nobody would need the highly resolved structural information. Stubbornly, the researchers went ahead anyway and succeeded getting the atomic resolution structure, overcoming size and irregularity challenges (see highlight Elusive HIV-1 Capsid). But the question remained: Is the atomic level structure of the huge HIV capsid made of 1,300 proteins useless? The HIV capsid is a closed container made of protein pentamers and hexamers, with a surface of continuously changing curvature. Two recent experimental-computational studies demonstrate now that the capsid structure is far from useless, in fact, it is a great treasure. The first study was published last year and showed that the human protein, Cyclophilin-A (CypA), involved in several diseases, interacts with the HIV capsid and affects the capsid's dynamic properties (see highlight HIV, Cells and Deception). In a second, recent study, guided by cryo-EM measurements and benefiting from large-scale molecular dynamics simulations with NAMD, researchers could resolve with new accuracy the binding of hundreds of CypA proteins on the capsid's surface. They found that CypA binds along high curvature lines of the capsid, which enhances stiffness and stability of the capsid, even though only about half of the capsid is actually covered by CypA. The limited levels of CypA stabilize and protect the viral capsid as it moves through the infected cell towards the cell's nuclear pore where nuclear proteins additionally bind to the capsid at places not covered by CypA and promote there uncoating and release of the capsid cargo into the nucleus. More information is available on our retrovirus website and in a news release.
