Viral Genetics

Mutations Much of our knowledge of viral reproduction and how it is regulated has depended on the isolation and characterization of virus mutants. Several kinds of mutants have been studied in viruses host-range mutants, plaque-type mutants, temperature-sensitive mutants, nonsense mutants, transposons, and inversions. 

Host-range mutations are those that change the range of hosts that the virus can infect. Host resistance to phage infection can be due to an alteration in receptor sites on the surface of the host cell, so that the virus can no longer attach, and host-range mutations of 

Temperature-sensitive mutations are those which allow a virus to replicate at one temperature and not at another, due to a mutational alteration in a virus protein that renders the protein unstable at moderately high temperatures. For instance, temperature-sensitive mutants are known in which the phage will not be replicated in the host at 43 °C but will at 25 °C, although the host functions at both temperatures. Such mutations are called conditionally lethal, since the virus is unable to reproduce at the higher temperature, but replicates at the lower temperature. 

Nonsense mutations change normal codons into nonsense codons. In viruses, nonsense mutations are recognized because hosts are available that contain suppressors able to read nonsense codons. The virus mutant will be able to grow in the host containing the suppressor, but not in the normal host. 

Transpositions several viruses are known which act essentially as transposons and transposition events involving viruses can lead to their genetic change. 

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Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

Tomalia, D. A. in Walsh, B. (ed.), Non-Viral Genetic Therapeutics Advances, Chal-langes and Applications for Self-Assembling Systems, IBC USA Conferences, Inc., Westborough, MA, 1996, pp. 1.2-1.2.36. 

Expression of the Viral Genetic Material. This occurs during the eclipse period, when the amount of infectious virus appears low. Several events occur during the eclipse phase ... 

Replication of the viral genetic material. The virus programs the machinery necessary to generate more copies of its own genetic material. In some cases, this may rely on the machinery from the infected cell, but in other cases, the virus may specify proteins that are necessary for the process. 

Synthesis of proteins for virus particles. Proteins that make the virus coat as well as those in the viral envelope are synthesized from instructions in the viral genetic information. Once these proteins are synthesized, all the components necessary for formation of new vims particle are present within the infected cell. 

Viruses are genetic materials enclosed in a protein coat. They show a very high specificity for a particular host cell, infecting and multiplying only within those cells. Viral genetic... 

DNA alone, or trapped inside a small fatty balloon that will melt into the cell s outer membrane, is also a possible vector. These vectors can carry large payloads, but because they do not include the viral genetic information, they are not very good at actually delivering the genetic material. 

Penetration and Uncoating. The virus enters the host cell either by passing directly through the cell membrane or by fusing with the host-cell membrane and releasing the viral genetic material into the host cell. Once inside the host cell, its proteolytic enzymes usually remove any coating that remains on the virus. 

Biosynthesis. When viral genetic material is released within the host cell, the virus takes control of the cell s molecular synthesizing machinery to initiate the biosynthesis of new viral enzymes and proteins. Different viruses exert their effects on the host cell in... 

Mechanism of Action. Acyclovir inhibits viral DNA replication by inhibiting the function of the DNA polymerase enzyme.42 This drug is taken into virus-infected cells and converted to acyclovir triphosphate by an enzyme known as viral thymidine kinase 42 The phosphorylated drug directly inhibits the function of the viral DNA polymerase, thus impairing the replication of viral genetic material. The virus also incorporates the drug into viral DNA strands, which halts further production of DNA because of the presence of a false nucleic acid.42... 

The exact cause of many cases of neoplastic disease is unknown. However, a great deal has been learned about possible environmental, viral, genetic, and other elements, or carcinogens, that may cause or increase a person s susceptibility to various types of cancer. Conversely, certain positive lifestyles, including adequate exercise, a high-fiber diet, and the avoidance of tobacco products, may be crucial in preventing certain forms of cancer. Of course, routine checkups and early detection play a vital role in reducing cancer mortality. 

Viral particle production processes by cell culture infection, cannot be characterized in such a simple way, since the final product - virus -does not result from a secondary metabolic pathway. However, it can be better described as a process redirecting the cell machinery towards viral particle production, which only happens after viral infection. The virus production process can be divided into two different steps. The first involves cell multiplication, which results from the conversion of culture medium substrates into cell mass. At the instant of viral infection, the cellular production unit no longer exists, since the viral genetic material forms a new production unit, initiating the second step of the virus production process. This production unit is the infected cell and is the producer of new viral particles. This production phase requires nutritional and metabolic conditions that are not observed during cell growth. These conditions are normally studied separately. Nevertheless, virus production... 

Little, S.R. Lynn, D.M. Ge, Q. Anderson, D.G. Puram, S.V. Chen, J. Eisen, H.N. Langer, R. Poly-beta amino ester-containing microparticles enhance the activity of non-viral genetic vaccines. Proc. Natl. Acad. Sci. U.S.A. 

Study bacterial genetics as well as viral genetics. And because viruses have no metabolism, their presence is indicated by the death of the host cell. 

Because viruses cannot grow or reproduce on their own, they are not considered to be alive. To survive, a virus must infect a host cell and take over its internal machinery to synthesize viral proteins and in some cases to replicate the viral genetic material. When newly made viruses are released, the cycle starts anew. Viruses are much smaller than cells, on the order of 100 nanometer (nm) in diameter in comparison, bacterial cells are usually > 1000 nm (1 nm= 10 meters). A virus is typically composed of a protein coat that encloses a core containing the genetic material, which carries the information for producing more viruses (Chapter 4). The coat protects a virus from the environment and allows it to stick to, or enter, specific host cells. In some viruses, the protein coat is surrounded by an outer membrane-like envelope. 

Viral infections are normally overcome by the patient s immune system. However, the advent of HIV infections and AIDS has led to the development of several new antiviral drugs. Antiviral drugs work by inhibiting the synthesis of viral DNA, RNA or proteins by reducing the release of viral genetic material inside host cells by interfering with viral penetration of host cell membranes and by interfering with attachment of virus to host... 

Autoimmunity. Autoimmune diseases are disorders of immune regulation in which several different factors (e.g. viral, genetic, hormonal, environmental) may each play a role. Autoimmune diseases may belong to any of the four Coombs and Cell classifications of hypersensitivity and include the production of autoantibodies, destructive inflammatory cell infiltrates in various organs, and deposition of immune complexes in vascular beds. Chemically induced autoimmunity may result from any of several possible mechanisms. These include the alteration or release of autoantigens, or the cross-reaction of the chemical with autoantigens, or alternatively a direct effect on the immune system via lymphocytes or macrophages (60). 

HIV-1 invades and destroys the CD4 positive cells of the immune system. Like other retroviruses, the life cycle requires incorporation of viral genetic material into the host genome. Subsequent transcription and translation events generate virus progeny. Release of the new virus particles is fatal to the host CD4 positive cell. A gradual depletion of immune cells occurs over a period of years and compromises the immune response to the extent that infections that normally would be relatively benign can become life threatening and deadly. 

Because viruses contain RNA and not DNA, replication of viral genetic material is not subject to the same error-checking and repair mechanisms as is cellular DNA. Thus, mutations in viral RNA are relatively more common, and viruses, should they be able to survive the mutations, can evolve rather quickly to circumvent cellular or therapeutic drug antiviral countermeasures. Antiviral defenses oftentimes recognize viral surface proteins as foreign bodies, and deal with them accordingly. Cytokines... 

Gratia, J.P. (2000) Andre Gratia a forerunner in microbial and viral genetics. Genetics, 156, 471 -476. 

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