Host cell replication

Viruses have no metabolism of their own they are only able to replicate in living host cells. Replication can be inhibited by virostatics. Generally, however, viruses cannot be completely inactivated as a rule, this is only possible by means of the body s own defences. The viruses... 

Despite the diversity in the structures of viruses and the types of host cell that are infected, there are several basic steps in the life cycle of all viruses infection (penetration of the virion or its nucleic acid into the host cell), replication (expression of the viral genome), maturation (assembly of viral components into virions), and release (the emission of new virions from the host cell). Because viruses usually possess only enough genetic information to specify the synthesis of their own components, each type must exploit some of the normal metabolic reactions of its host cell to complete the life cycle. For this reason there are numerous variations on these basic steps. This point can be illustrated by comparing the life cycles of two well-researched viruses the T4 bacteriophage and the human immunodeficiency virus (HIV). 

Various viruses encode proteins with sequenee homology to host proteins which are known to be involved in host defense functions. Viruses pirate and modify key immunoregulatory molecules, by use of molecular mimicry, to elude the Immune system (Murphy, 1997). Viruses also encode proteins that exploit or alter their host cells, replicate or induce migration for virus dissemination. Interestingly, DNA viruses such as the Herpesviruses (Cytomegalovirus (CMV), human herpesvirus (HHV-6 and 7), herpesvirus Saimiri (HVS) and Kaposi s sarcoma-associated Herpesvirus (KSHV)) all express GPCRs (Table 2). 

The TCID50 values represent the drug concentration (pM) required to inhibit 50% of host cell replication. ND not determined. 

In addition to binding to sialic acid residues of the carbohydrate side chains of cellular proteins that the virus exploits as receptors, hemagglutinin has a second function in the infection of host cells. Viruses, bound to the plasma membrane via their membrane receptors, are taken into the cells by endocytosis. Proton pumps in the membrane of endocytic vesicles that now contain the bound viruses cause an accumulation of protons and a consequent lowering of the pH inside the vesicles. The acidic pH (below pH 6) allows hemagglutinin to fulfill its second role, namely, to act as a membrane fusogen by inducing the fusion of the viral envelope membrane with the membrane of the endosome. This expels the viral RNA into the cytoplasm, where it can begin to replicate. 

Short replication cycles that may be completed within a few hours, a large amount of viral progeny from one infected host-cell, as well as the general inaccuracy of viral nucleic acid polymerases result in an evolution occurring in fast motion, allowing rapid adaptation of viruses to selective pressures (see chapter by Boucher and Nijhius, this volume). Generalizing, it can be stated that any effective antiviral therapy will lead to the occurrence of resistance mutations. A well studied example... 

Bacterial plasmids are small, circular, duplex DNA molecules whose natural function is to confer antibiotic resistance to the host cell. Plasmids have several properties that make them extremely useful as cloning vectors. They exist as single or multiple copies within the bacterium and replicate independently from the bacterial DNA. The complete DNA sequence of many plasmids is known hence, the precise location of restriction enzyme... 

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