Virus principle

CDC. Prevention and treatment of mberculosis among patients infected with human immunodeficiency virus Principles of therapy and revised recommendations. MMWR 1998 47 1-58. 

KoudeUta, K.J., Manchester, M., 2010. Chemically modified viruses principles and applications. Curr. Opin. Chem. Biol. 14, 810-817. 

In this chapter we will examine the construction principles of spherical viruses, the structures of individual subunits and the host cell binding properties of the surface of one of the picornaviruses, the common cold virus. 

Two basic principles govern the arrangement of protein subunits within the shells of spherical viruses. The first is specificity subunits must recognize each other with precision to form an exact interface of noncovalent interactions because virus particles assemble spontaneously from their individual components. The second principle is genetic economy the shell is built up from many copies of a few kinds of subunits. These principles together imply symmetry specific, repeated bonding patterns of identical building blocks lead to a symmetric final structure. 

Caspar, D.L.D., Klug, A. Physical principles in the construction of regular viruses. Cold Spring Harbor Symp. Quant. Biol 27 1-24, 1962. 

Appropriately designed prodrugs, for example, phosphonoamidates (Lee et al. 2005), may allow acyclic nucleoside phosphonates such as tenofovir to be specifically targeted at tissues, that is, lymphatic tissue, where the virus (i.e., HIV) replicates. This principle has been recently extended to another nucleotide analogue, GS-9148 (Cmiar et al. 2008) and its phosphonoamidate prodrug, GS-9131 (Ray et al. 2008). 

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

A broad and vigorons T cell response generally accompanies elimination of HBV as well as HCV infection. By contrast, patients with chronic hepatitis B or C tend to have late, transient, or narrow T cell responses. In a long-term follow-up of HBV-infected patients receiving HPC transplants from HBV-immune individuals, 20 of 31 recipients cleared their HBV infection (Hui et al. 2005). In principle, these results encourage the development of adoptive T cell transfer strategies for the treatment of chronic viral hepatitis. However, it is still controversial whether induction of an efficient T cell response is the cause or the consequence of viral clearance. Furthermore, T cell responses do not only contribute to virus control but also to disease pathology (Rehermann and Nascimbeni 2005). 

This section considers, in three separate chapters, the anatomy and physiology of bacteria, fungi and yeasts, and viruses, together with a survey of the characters of individual members of these groups likely to be of importance to the applied field covered by this book. Additional information is provided about more rapid methods for detecting bacteria. The final chapter in this section (Chapter 4) considers the principles of microbial pathogenicity and epidemiology. 

Sterilization, Disinfection and Cleaning of Medical Equipment Microbiology Advisory Committee (1993) Guidance on Decontamination fixMnttie Microbiology Advisory Committee to Department of Health Medical Devices Directorate. Part 1 Principles. London HMSO. van Bueren J., Salman H. Cookson B.D. (1995) The Efficacy of Thirteen Chemical Disinfectants against Human Immunodeficiency Virus (HIV). Medical Devices Agency Evaluation Report. 

The testing of disinfectants for virucidal activity is not an easy matter. As pointed out earlier (Chapter 3), viruses are unable to grow in artificial culture media and thus some other system, usually employing living cells, must be considered. One such example is tissue culture, but not all virus types can propagate under such circumstances and so an alternative approach has to be adopted in specific instances. The principles of such methods are given below. 

Plaque assays, at present, apply to only a very limited number of viruses, e.g. poliovirus, herpes virus, human rotavirus. The principle ofthese assays is as follows test virus is dried on to coverslips which are immersed in various concentrations oftest disinfectant... 

Duck hepatitis B virus (DHBV) has been proposed as a possible model for the inactivation of human HBV by chemical disinfectants. The principle of the test method uses viral DNA polymerase (DNAP) as a target, total inhibition in vitro of DNAP by chemical disinfectants being predictive of inactivation of infectivity in vivo. 

The antiviral activity spectrum of the ddN analogues should, in principle, extend to all retroviruses as well as hepadnaviruses [i.e., hepatitis B virus (HBV)], since HBV, like retroviruses, replicates through an RNA template-driven RT process. Indeed, various ddN analogues (particularly, the L-enantiomeric forms 3TC, FTC, and L-DDC) have been shown to inhibit HBV replication [36-38]. Consequently, 3TC is, at present, pursued as a potential drug candidate for the treatment of both HIV and HBV infections. 

Several enveloped viruses, and some physical gene transfer techniques such as electroporation, deliver the nucleic acid into the cell by direct crossing of the cell membrane. Lipid-based, enveloped systems can do this by a physiological, selfsealing membrane fusion process, avoiding physical damage of the cell membrane. For cationic lipid-mediated delivery of siRNA, most material is taken up by endo-cytotic processes. Recently, direct transfer into the cytosol has been demonstrated to be the bioactive delivery principle for certain siRNA lipid formulations [151]. 

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