Virology BSCI 437: Lecture 1Impact: It is important to study viruses because:· Many important infectious diseases that afflict humankind are caused by viruses. These can befatal, uncomfortable and very contagious, cause congenital defects, or carcinogenic. · Viruses can also affect the food supply, infecting crop plants and food animals.· The relatively simple nature of viruses makes them useful as model systems for many of thebasic problems in biology. History: · Evidence of viral diseases in humans date back to 1500 BC: Polio, Smallpox, Rabies. (Figureof Egyptian Polio, fig. 1.1., Tulip Mosaic Virus, Smallpox, 1.3)· The existence of viruses became evident at the end of the 19th century. The newly acquiredexpertise in handling of bacteria led to the germ theory of disease. · Viruses are Small!· Ultrafiltration methods made it clear that the causative agents of some diseases were evensmaller than bacteria. (Filters figure, 1.6) · Infection by ultrafiltrate: The first example of this was demonstrated by Iwanowski withTobacco Mosaic Virus (1892), followed by Loeffler and Frosch with Foot and Mouth Disease(1898). · In 1898, Beijerinck introduced the term “virus” (Latin for “poison”) to the literature. The term“Virus” became the operational definition of particulate infectious agents that are smaller thanbacteria and which are unable to multiply outside of living cells.· In 1911, Rous discovered a virus that produced malignant tumors in chickens (Rous SarcomaVirus). This “Oncovirus’ turns out to be the first Retrovirus discovered. Discovery of new viruses was very rapid.· During the next 25 years, virology diverged into three areas: Plants, bacteriophages andanimal viruses. · The ability to isolate large amounts of viruses from plants permitted extensive chemical andphysical analyses, eg: o The first demonstration that viruses consisted of proteins and nucleic acids. o The crystallization of TMV by Stanley (1935) was a paradigm shift in that itdemonstrated that agents able to reproduce in living cells could also behave likemacromolecules.· Bacteriphage research initially focused on the hypothesis that these viruses could be used forantibacterial therapies, i.e. that they could be injected into people to destroy bacteria inside ofthe body. Although this proved to be untenable, this work set the technological foundation formolecular biology as we know it. Examples include the discovery that nucleic acids are themolecules of genetic inheritance (Hershey & Chase 1952, also credit Oswald, MacLeod andMcCarthy, 1944), the first model systems for DNA replication (M13), control of geneexpression and recombination (λ), discovery of mRNA, the elucidation of the factors thatcontrol initiation and termination of both transcription and translation of genetic information,and the discovery of restriction endonucleases.· Animal virus research concentrated on the pathogeneis of viral infections and epidemiology.The need to study animal viruses spurred the development of techniques for growing animalcells in vitro. Animal virus systems also played a large role in the development of immunology.1· The “New” Molecular Biology is founded on Virology. o Understand cellular functions such as DNA (SV40) replication and repair, o RNA splicing (adenoviruses), o translation (picornaviruses, poli), o protein-protein interactions, o gene expression (retroviruses), o Cancer and malignancy (Tumor viruses, papilloma and oncogene carrying retroviruses). Oncogenes (genes within cells that are associated with cancer when they mutate or are over or under-expressed depending on the particular oncogene) were originally discovered in retroviruses. The virus captured these genes early onin their evolution from cells they infected. Expression of these genes by the virus in the infected cell can lead to the cell becoming cancers although, because of the complex nature of cancer, this is a rare event. Still, a single cancerous cell is all that is required to start a tumor. · Therapeutics: Vectors to introduce foreign genes into bacteria (insulin) or animals (gene therapy and vaccine development. Commonly used vectors are based on poxviruses, retroviruses, adenoviruses (among others). A particular vector may be able to home in on particular cell types (ex. Adenovirus-respiratory tract cells, retrovirus-immune system cells) while others may be more general.The Origin of Viruses. Three possible origins:· Products of regressive evolution from free living cells. Best candidate are the Poxviruses.· Derived from cellular genetic material that has acquired the capacity to exist and functionindependently.· Leftovers from the pre-biotic RNA world.Definition of a Virus. A genetic element containing either RNA or DNA that is able to alternate between intra- and extracellular states, the latter being the infectious state. Viruses are obligate intracellular parasites. They are absolutely dependent on the host cells’ synthetic and energy-yielding apparatus. Viruses consist of a nucleic acid genome that is protected by a protein component (typically surrounded by a protein shell called a nucleocapsid). Frequently, there is a second outer shell composed of lipids and proteins. Virus characteristics:1. Virus is an infectious agent and obligate intracellular parasite.2. Virus infectious cycle includes a phase in which the agent consists of a virion. The virion consists of RNA or DNA coated with one or more proteins (capsid structure) which is sometimes coated with a membrane containing lipid and glycoproteins.3. A virus can initiate another infection when transferred to a suitable host.4. A virus carries genetic information in the form of RNA or DNA. This genomic nucleic acid carries information which redirects the genetic and metabolic apparatus of the infected cell to produce virions.Terms: 2Virion- Morphologically complete (mature) infectious virus particle.Pathogen- Biological disease agent.Bacteriophage- Viruses that infect bacteria. Phage is Greek for eating, since bacteriophage produced hole on lawns of bacteria.Virulence- the ability of an infectious agent to produce disease. Many viruses are virulent sometimes and asymtomatic at other times. The Herpes virus Epstein Barr virus (EBV) for example generally infects people but causes no disease. However, in some, especially immune compromised
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