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Impact: It is important to study viruses because:
•Many important infectious diseases that afflict humankind are caused by viruses. These can be fatal, uncomfortable and very contagious, cause congenital defects, or carcinogenic.
•Viruses can affect the food supply: crop plants and food animals.
•The relatively simple nature of viruses makes them useful as model systems for many of the basic problems in biology.
Virology, lect. 1.
Viruses in antiquity: polio
Viruses in antiquity: Ramses V had smallpox
Tulip mosaic virus: Varigated tulips first described in 1576
Smallpox: first described in India, 5th century B.C.
Viruses are small!
Filter systems used to characterize
Tobacco mosaic virus: Demonstration of
infectivity of ultrafiltrate by Mayer
The pace of early discovery of new infectious agents
Plants, bacteriophages and animal viruses: the three general areas
Advances from plant virology
The ability to isolate large amounts of viruses from plants permitted extensive chemical and physical analyses, e.g.:
•The first demonstration that viruses consisted of proteins and nucleic acids.
•The crystallization of TMV by Stanley (1935) was a paradigm shift in that it demonstrated that agents able to reproduce in living cells could also behave like macromolecules.
· Initial focus on the hypothesis of bacteriophage as antibacterial therapies.· Although this proved to be untenable, this work set the technological foundation for molecular biology as we know it. Examples include:· Discovery that nucleic acids are the molecules of genetic inheritance (Hershey & Chase 1952, also credit Oswald, MacLeod and McCarthy, 1944), · The first model systems for DNA replication (M13), · Control of gene expression and recombination (λ), · Discovery of mRNA· Elucidation of the factors that control initiation and termination of both transcription and translation of genetic information, · Discovery of restriction endonucleases.
·Pathogenesis of viral infections and
·The need to study animal viruses spurred the development of techniques for growing animal cells in vitro. -HeLa cells
·Animal virus systems also played a large role in the development of immunology.
Animal virus research
Understanding of cellular functions e.g.:•DNA replication and repair (SV40),
•RNA splicing (adenoviruses), •Translation (picornaviruses, poli), •Protein-protein interactions, •Gene expression (retroviruses), •Cancer and malignancy.
•Oncogenes originally discovered in retroviruses.
•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-mmune system cells) •others may be more general.
The “New” Molecular Biology is founded on
The Origin of Viruses
Three possible origins:1. Products of regressive
evolution from free living cells. Best candidate are the Poxviruses.
2. Derived from cellular genetic material that has acquired the capacity to exist and function independently.
3. 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.
• Virion- 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.
Virus characteristics• A virus is an infectious agent and
obligate intracellular parasite.
• 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.
• A virus can initiate another infection when transferred to a suitable host.
• 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.
1. Cell attachment – binding to a cell surface receptor.
2. Entry via receptor—mediated endocytosis.
3. Release of genome into cytoplasm via membrane fusion.
4. Transcription of viral mRNAs and of new viral genomes (RNA viruses)
5. Viral protein synthesis and assembly of provirus.
6. Maturation of viral particle.
7. Release of virus from cell.
8. Evasion of host defense and transmission to new host.
The common tasks faced by (almost) all viruses.
Effects on Host Cells
• Inhibition of Host Macromolecular Biosynthesis.
• Changes in Regulation of Host Gene Expression.
• Appearance of New Antigenic Determinants on the Cell Surface.
• Cell Fusion.
a) HIV-1 infected T-cell
b) Cytoplasm surrounding multiply nucleated syncytium