Viruses 1 Viruses Viruses are important to biologists for several reasons. They are the simplest form of life. Indeed they are so simple that they exist on the borderline between the living and the inanimate, non-biological world. Viruses also reveal much about more complex biological entities including cells because viral replication is governed by the same principles that govern the lives of cells. Finally, viruses are responsible for many human diseases including influenza and AIDS. Some evolutionary biologists argue that all organisms on the planet are simply complex devices whose sole purpose is to make more copies of their own genomes. Viruses take this notion to the extreme. They are mostly DNA that happen to be wrapped in a coating (termed a capsid). The capsid affords protection for the viral genes and allows viral genes to gain entrance to appropriate host cells. Viruses exist at the border of the living and non-living because they are unable to replicate on their own. They are obligate parasites in the sense that they can only replicate after they have invaded and parasitized a host cell. Because viral genomes could be isolated from the genomes of the infected cells, viruses were a good source of pure DNA. This explains why viruses were studied so intensively before the advent of gene cloning. For example, the SV40 virus, a double-stranded DNA virus, carries approximately five genes in its genome and the viral DNA molecules were readily separated from the DNA of the monkey cells infected by this virus. (Recall that the host cell genome carries about thirty thousand genes.) The origins of viruses are even more obscure than the origins of cellular forms of life. Since viruses are obligate cellular parasites, we can only assume that they evolved later than cells, either as degenerate cells or as renegade cellular genes that learned to manipulate the replication machinery of the cells in which they arose. Viral genomes evolve more rapidly than the genomes of cellular organisms. This rapid genetic change has obscured or erased any relationships that may have existed between various types of viruses and might have been used to illuminate their ancient roots. The viruses that parasitize bacterial cells (bacteriophages) and those that parasitize animal cells (animal viruses) operate on identical principles, even though the details of their genes and the organization of their genomes give no hint of relatedness. We will focus on animal viruses, the mechanisms by which they replicate, and the consequences of their replicative strategies on their disease-causing abilities. Strategies for Virion Formation Like bacteriophages, some animal viruses use DNA while others use RNA molecules to carry their genetic information. Virus particles, often termed virions are assembled through two strategies. The simplest strategy involves wrapping the viral genome in a protein coat or capsid. Without exception, the capsid proteins are encoded by the viral genome.Viruses 2 A more complex strategy for constructing a virion is used by the majority of animal cell viruses. As above, their genomic DNA or RNA is wrapped in a protein coat. This protein coat:nucleic acid complex (sometimes called a nucleocapsid), is then wrapped in a second outer coat, a lipid membrane. The lipid membrane is usually acquired as the viral nucleocapsid exits the host cell. As it is being pushed though the host plasma membrane a patch of this membrane becomes wrapped around the nucleocapsid. Hence, the membraneous outer layer of the virion is of host cell origin. A wide variety of animal cell viruses use this membrane-scavenging strategy for forming their virions. Among these are the influenza virus, encephalitis virus, smallpox virus, rabies virus, herpes virus, and the human immunodeficiency virus (HIV). In each case, the membrane surrounding nucleocapsid is studded with an array of virus-encoded proteins. Usually the N-termini of these proteins protrude outward into the fluid outside of the viral particle; the C-termini often contact the nucleocapsid inside the membrane. Since lipid bilayers are easily dissolved by detergents, these lipid-containing virions are readily inactivated by soaps and detergents while the purely proteinaceous virions are quite resistant to soaps. This explains why most gastrointestinal viruses (including poliovirus) have virions that are purely protein. Their virions can resist the strong detergents present in the liver bile that is constantly introduced into the small intestine to aid with digestion. Lipid containing virions are inactivated by the bile and cannot infect cells further down in the intestine. All virus capsids, whether purely protein or protein:lipid composites share two traits: they must protect the nucleic acid inside from substances that might destroy the viral genome, and they must facilitate the adsorption (attachment) of the virion to the surface of the host cell. The invasion of a cell by a virus particle always depends upon a specific and tight binding of the virus particle to some surface component of the host cell's plasma membrane. Viruses have evolved the means to recognize and bind tightly to cell proteins. Invariably, these tethering sites on the host cell are normal cell proteins. Each type of virus takes advantage of different proteins to gain entry to a specific type of host cell. In the case of purely proteinaceous capsids, the capsid proteins have affinity for one or another of the host cell's surface molecules; in the case of lipid-containing virions, the viral proteins extending from the membrane can attach to a host cell surface protein. This adsorption must be followed by penetration where the virus succeeds in crossing the plasma membrane and entering the cytoplasm of the host cell. Since the host cell is constantly internalizing its own membrane proteins and recycling them back to the surface, many viruses hitch a ride on these host cell proteins to gain entrance into the cell. Other viruses, including HIV, have developed the means to fuse themselves to the host cell thereby allowing the nucleocapsid direct access to the host cell interior. Once inside, some viruses complete their entire replication cycle inside the cytoplasm, yet others may move into the nucleus to replicate.Viruses 3 Viral Replication Strategies The life cycle of most viruses is designed to maximize the production of progeny virus
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