Viruses, defence

Gale M Jr, Eoy EM (2005) Evasion of intracellular host defence by hepatitis C virus. Nature 436 939-945... 

Two major advantages stem from the use of live vaccines. Firstly, the immunization mimics a natural infection such that only a single exposure is required to render an individual immune. Secondly, the exposure may be mediated through the natural route of infection (e.g. oral) thereby stimulating an immime response that is appropriate to a particular disease (e.g. secretory antibody as primary defence against poliomyelitis virus in the gut). 

The progression of human immunodeficiency virus (HIV) towards its more advanced stages is accompanied by increasing body stores of iron. Iron accumulates in macrophages as well as microglia, endothelial cells and myocytes. The iron burden is especially intense in the bone marrow, brain white matter, muscle and liver. Such excesses of iron will enhance oxidative stress, impair several already compromised immune defence mechanisms and directly promote the growth of microbes (Boelaert et ah, 1996). 

Myeloperoxidase is an extremely potent, antimicrobial protein that is present in neutrophils at up to 5% of the total cell protein. Its role in the killing of a wide range of bacteria, fungi, viruses, protozoa and mammalian cells (e.g. tumour cells) is well established from in vitro studies. It also plays an important role in the inactivation of toxins and the activation of latent proteases, as well as in other functions described in section 5.4.1. In view of this apparent central role in neutrophil function during host defence, one would think that any deficiencies in this enzyme would have disastrous consequences on the ability of the host to combat infections. Until the early 1980s, this key role for myeloperoxidase in host protection seemed substantiated by the extremely low incidence of reports of patients with deficiencies of this enzyme. Indeed, up to this time, only 15 cases from 12 families had been reported worldwide. Sometimes these patients were asymptomatic but often suffered Candida infections, particularly if their myeloperoxidase deficiency was also associated with diabetes mellitus. 

Cytokines are peptides that are produced and secreted by cells of the immune system. They organise the immune response to invasion by a pathogen by communicating between the different cells. They are synthesised in the immune cells as precursor proteins (pro-proteins) from which a peptide is removed by a proteolytic enzyme to produce the active cytokine, prior to secretion. This enzyme is a serine protease. Perhaps surprisingly, some viruses are capable of synthesising serpins which inhibit this enzyme in the immune cells, so that secretion does not occur and communication and integration of the immune response to the viral infection is lost. This is one of many biochemical mechanisms by which pathogens can reduce or overcome the defence mechanisms of the host (Chapter 17). 

Waterhouse, P.M., Wang, M.B., and Lough, T. (2001). Gene silencing as an adaptive defence against viruses. Nature 411 834-842. 

Other issues regarding the large-scale application of plant viral-based vectors include their ability to infect a wide spectrum of hosts, as well as to tolerate a variety of adverse enviromnental conditions and host defence responses. To assist in the replication of the virus at optimal levels under these conditions in the field, new varieties of host plants (transgenic and nontransgenic alike) that will allow vigorous virus infection must be developed work is currently under way. 

Figure 11. The error threshold of replication and mutation in genotype space. Asexually reproducing populations with sufficiently accurate replication and mutation, approach stationary mutant distributions which cover some region in sequence space. The condition of stationarity leads to a (genotypic) error threshold. In order to sustain a stable population the error rate has to be below an upper limit above which the population starts to drift randomly through sequence space. In case of selective neutrality, i.e. the case of equal replication rate constants, the superiority becomes unity, Om = 1, and then stationarity is bound to zero error rate, pmax = 0. Polynucleotide replication in nature is confined also by a lower physical limit which is the maximum accuracy which can be achieved with the given molecular machinery. As shown in the illustration, the fraction of mutants increases with increasing error rate. More mutants and hence more diversity in the population imply more variability in optimization. The choice of an optimal mutation rate depends on the environment. In constant environments populations with lower mutation rates do better, and hence they will approach the lower limit. In highly variable environments those populations which approach the error threshold as closely as possible have an advantage. This is observed for example with viruses, which have to cope with an immune system or other defence mechanisms of the host.

Persistent and severe cold sores may be exacerbated by a range of underlying issues, such as fatigue, emotional or stress-related problems, a cold (or other viruses which may weaken the body s defences), and menstrual periods (which is not directly applicable to this patient). Particular weather conditions, such as strong sunlight (the use of sun-block may be an issue) or wind, may make the cold sore worse. Triggers are different for each person, and any underlying issues should be referred to the patient s doctor. 

Anti-viral drugs use mechanisms that interfere with nucleic acid and protein synthesis, inhibiting their attachment to and penetration of host cells. Because the viruses frequently adapt their structures, their elimination is difficult. A research team in Cambridge19 are looking at what they call a mutator protein . This protein is made by our own cells and is released to sneak inside certain viruses and cause chaos and mutations in their genome. Unfortunately the AIDS virus has evolved a defence against this process, but it is useful for other viruses. 

Chemokine accumulation occurs in autoimmune degenerative disease such as multiple sclerosis and in allergic inflammatory diseases such as asthma. Various viruses produce CH antagonists that interfere with the CH-mediated defence system and HIV-1 infects cells via the CCR5 receptor. 

Murray, A. G. (1995). Phytoplankton exudation Exploitation of the microbial loop as a defence against algal viruses.Plankton Res. 17(5), 1079—1094. 

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... 

Morrow, C.D. Novak, M.J. Ansardi, D.C. Porter, D.C. Moldoveanu, Z. Recombinant viruses as vectors for mucosal immunity, defence of mucosal surfaces pathogenesis, immunity and vaccines. In Current Topics in Microbiology and Immunology Kraehenbuhl, J.P., Neutra, M.R., Eds. Springer-Verlag Berlin, 1999 236, 255-273. 

Interferons are a group of pleiotropic cytokines with important proinflammatory functions required in defence against infections with bacteria, viruses and multicellular parasites along with fundamental functions in other processes such as cancer immuno-surveiUance, immune homeostasis and immunosuppression [209]. IFNs are classified into type I and type II IFNs [210]. Type I IFNs comprise multiple alpha IFNs (IFN-a), and single IFN-, -e, -k, - and -oo subtypes, all encoded by different genes. Type IIIFN consists of a single IFN-y gene. 

Adaptive immunity provides a defence against some of the pathogens that avoid the innate immune system and can mount an attack against the evolving and ever changing characteristics of disease-causing organisms, e.g., different strains of bacteria and viruses, such as those that cause influenza. 

It is well known that the superoxide anion from neutrophils kills bacteria and virus and plays an important role in biological defence. It is also well known that calcium ion is a intracellular mediator. But details about the relationship between superoxide anion and calcium ion are not clear. To reveal their relationship, it is important to measure the time-course of calcium ion concentration and superoxide anion genaration from neutrophil-like cells in real time. We have developed a novel method to measure fluorescence and chemiluminescence simultaneously in real time to investigate function of the cells. 

---