Molecular biology and genetics are an integral part of biosecurity problems.
It is important to concentrate our attention on some of the most perspective
1) The investigations that shed new light on the mechanisms which allow viruses to overcome protective systems of organism; the revealation of genetic complexes which determine a close combination of high epidemic potential and virulence of the most dangerous viruses; careful estimation of adequate transfer the data obtained in investigations with experimental animals to human beings.
2) The danger of rapid development of investigations providing the possibility of long-term manipulation on human state of mind.
Of especial importance are the investigations of monogenic virus factors blocking key defense reaction. The examples are recent data about virus blockators of interferon production, migration of HLA 1 complexes to the surface of infected cell etc.
Some paradox of severe virus diseases is the existence of perverted immune reaction after infection. The example is the reinforcement of virion binding by complex of antibody with complement C1q.
A new approach to the problem of molecular mimicry is necessary. The idea of high degree of similarity between some host and virus antigens seems too superficial now. Only an identity of small epitop sequences exhibited on the surface of the antigen is a real cause of immune barrier overcoming. But the search of such sequences is a very difficult task. Computer-analytical comparison has restricted effectiveness: it is difficult to predict exposed positions of the sequence. It is also impossible to take into account posttranscriptional modifications (if we compare the nucleotide sequences). The absence of "preliminary addresses" hampers direct immunological search. More effective is the revelation of those molecular targets of virus which are identical or close to host regulatory compounds or their receptors. The example of such approach is the similarity between some sequences of viral haemagglutinine and plasminogen activator.
For epidemic potential of virus the intensive reproduction in human epithelial tissues is especially important. But corresponding investigations on surviving human tissues are very restricted. We have to stress that traditional usage of transformed cell lines or even surviving cells from experimental animals may lead to erroneous results.
The experiments of viruses reproduction in surviving human tissues are also
necessary for correct estimation of adequate transfer to human beings of the
results obtained in animals.
There is some deficit of information about molecular factors determining the stability of RNA viruses in external media and on mucous membranes.
It is generally accepted that RNA-viruses are the most dangerous as the source of new epidemics. Mechanisms of high probability of their mutations and recombination's between relative strains must be the object of investigations by means of new approaches (e.g. ODN method).
The second direction of especially important molecular investigations on global level is connected with rapid development of methods for manipulation on human state of mind. Apart of numerous substances having short-term action on the highest functions of brain new direction have arisen recently: the induction of autoantibodies against endogenous regulatory compounds which results in very long-tern delicate changes of the behavior. Several examples are discussed in the communication…
The importance of molecular biology and genetics participation in biosecurity
problems is obvious, but it is necessary to concentrate our common efforts
on the most actual directions. Some of them have been demonstrated above.
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5. Sanderson S.D., Cheruku S.R., Padmanilayam M.P. et al. "Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant", Int. Immunopharmacol., 2003, v. 3, N 1, p.137-146
6. Williams B.G., Sen G.C. "A viral on/off switch for interferon", Science, 2003, v. 300, p.1100-1001
7. Basler C.F., Mikulasova A., Martinez-Sobrido L. et al. "The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3", J. Virology, 2003, v. 77, N 14, p. 7945-7956
8. Takada A., Feldman H., Ksiazek T.G. et al. "Antibody-dependent enhancement of Ebola virus infection", J. Virology, 2003, v. 77, N 13, p. 7539-7544
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Russian Workshop on Biological Security
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