Host cell delayed

Potentially, interferon is an ideal anhviral agent in that it acts on many different vimses and is not toxic to host cells. However, the exploitation of this agent in the treatment of viral infechons has been delayed by a number of factors. For example, it has proved to be species-specific and interferons raised in animal sources offered little protechon to human cells. Human interferon is thus needed for the treatment of human infechons and the produehon and purificahon of human interferon on a large scale has proved difficult. The inserhon of human genes for interferon into E. coli has resolved the produehon problems (Chapter 24). Clinical trials have demonstrated that interferon prevents rhinovirus infeehon and has a beneficial effect in herpes, cytomegalovims and hepahtis B vims infechons. 

Within each host cell system, several independent isolates and laboratory variant strains are available, and the efficiency of expression can vary between them for reasons that are not always understood. For example, there are several independently isolated strains of E. coli, which vary in their ability to express the same protein using the same vector. Thus, it is routine to test several strains for optimal production, and this is usually achieved by screening a bank of available strains. In addition, notably in the E. coli system, there are several mutant strains which may be used to increase product yield and improve fermentation characteristics. Such mutants may have deficiencies in proteases, resulting in increased stability of the expressed protein (Kresze, 1991), cell-wall mutations permitting better secretion characteristics (Le and Trotta, 1991), or resistance to bacteriophages which can lyse bacteria leading to losses and delays in large-scale fermentation. 

Most of the research in this field has been done with the prototype vesicular stomatitis virus because of its rapid growth to high titer in a wide variety of cell types and relative ease for purifying large amounts of homogeneous virus particles. VSV rapidly kills many host cells and even more rapidly shuts off cellular macromolecular synthesis (Week and Wagner, 1978). On the other hand, infection of cells with rabies virus results in only a delayed cytopathic effect and dis-... 

Several strains of HSV-2 have been reported to cause a more rapid decline of host cell protein synthesis than certain HSV-1 strains (Powell and Courtney, 1975 Pereira et al., 1977 Hill et ai, 1983) suggesting the generalization that HSV-2 causes early, virion-associated shut-off and HSV-1 only delayed, expression-dependent shutoff. However, the work described above (Nishioka and Silverstein, 1978 Fenwick and Clark, 1982 Read and Frenkel, 1983) has demonstrated that some strains of HSV-1 can cause early shut-off. Sometimes contrasting results have been obtained. HSV-l(KOS) failed to cause early shut-off in Friend leukemia cells (Hill et ai, 1983) but did so in HEp-2 cells (Read and Frenkel, 1983). One strain of HSV-2, HG52, does not cause early shut-off, at least in Vero cells (unpublished observation). The possible role of the host in succumbing to or resisting early shut-off has not been studied systematically and temperature may also be critical (Hill et ai, 1983). HSV-l(F) caused early shut-off at 37°C but not at 39°C, whereas, HSV-2(G) was fully effective at 39°C (Fenwick and Clark, 1982). 

The mutant L37 cbrA21 is affected as regards to its iron uptake pathway mediated by the siderophore achromobactin. Because this mutation results in derepression of the chrysobactin mediated iron transport pathway, the mutant is probably less susceptible to iron deprivation than wild-type cells are, when entering the host. This results in a delay in Pels production thus leading to delayed symptoms, as reported by Sauvage and Expert (1994). 

Viruses may also cause latent infection of a host. In a latent infection, there is a delay between infection by the virus and the appearance of symptoms. Fever blisters (cold sores), caused by the herpes simplex virus, result from a latent viral infection the symptoms reappear sporadically as the virus emerges from latency. The latent stage in viral infection of an animal cell is generally not due to the integration of the viral genome into the genome of the animal cell, as is the case with latent infections by temperate bacteriophages. 

The involvement of mast cells in host protection against nematode infection is well characterized in T. spiralis infection. W/Wv mice exhibited a significant delay in worm expulsion, and treatment with either anti-SCF or anti-SCF receptor monoclonal antibody dramatically inhibited mast cell responses and expulsion of T. spiralis for the duration of treatment (Donaldson et al., 1996). W/Wv mice also lack interstitial cells of cajal and intraepithelial y T cells (Maeda et al., 1992 Puddington et al., 1994), which may contribute to the impaired response in these animals (see below). However, supporting evidence of a role for mast cells in protection against T. spiralis comes from studies in which overexpression of IL-9 in mice (which is known to influence the mast cell responses see above) resulted in an extremely rapid mast cell-dependent expulsion of T. spiralis (Faulkner et al., 1997). 

Other acceptable assays include drug effect on NK cell function in vitro bastogenesis, cytotoxic T cell function, cytokine production, delayed-type hypersensitivity, host resistance to infections or implanted tumors. 

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