[Modeling in virology].
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Biomedical subjects
Publications and source records attributed to G M Nazarova.
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A system of means of genetic information transmission (MGIT) modeling the main features of modes of virus reproduction as well as an algorithmic approach to its construction and means of its schematic representation are proposed. The system may be used as the basis for virus classification including taxonomic categories above the family level and for the study of possible evolution relationships between virus groups. One of the variants of virus macroevolution model is described.
A complex analysis of virus groups was carried out in order to find out possible ways of their macroevolution. The analysis was based on the detection of similar groups of viruses which could be considered to be evolutionally close. The similarity was evaluated both by a complex of virus properties (physicochemical, morphological, etc.) and using systemic analysis of means of genetic information transmission (MGIT) describing the features of replication and transmission properties. The developed systemic approach using the analysis of the MGIT system and integral differences between viruses by the totality of their properties helped to form models of virus evolution taking into account, in particular, their mono- or polyphyletic origin, more definite knowledge on pravirus(es) MGIT, etc. A monophyletic model of macroevolution of viruses was constructed.
Mathematical methods were used to analyse the data on the antigenic specificity of H2 subtype hemagglutinin of human and avian influenza A viruses. This approach allowed the evaluation of possible evolutional relationships in this little-studied group of viruses. Influenza A (H2) viruses isolated from birds in the USA were found to represent a sufficiently isolated group, whereas European avian strains (A/duck/Germany/1215/73, A/pintail duck/Primor'e/695/76, A/duck/Marseilles/46/76) were close to "human" viruses. The A/Leningrad/1468/65, A/laughing gull/New Jersey/75/85, and A/pintail duck/Alberta/2728/77 strains represent marked antigenic variants apparently rather far gone as a result of hemagglutinin drift.
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Inoculation of CBA mice with pathogenic influenza A/PR8/34 (H1N1) virus and non-pathogenic A/Krasnodar/101/59 (H2N2) virus demonstrated that the pathogenic strain enhanced the synthesis of serum interferon and activated the function of normal killers, but had a relatively low capacity of causing in vitro proliferative response of spleen lymphocytes of intact and in vivo primed animals. In contrast, the nonpathogenic virus had less marked interferon-inducing capacity and that of activating normal killers, but induced a very high proliferative response of lymphocytes in culture.
The data are presented dealing with the construction of algorithm of numerical classification of RNA- and DNA-containing viruses of vertebrates. The possibility of using of a limited number of parameters with certain coefficients was demonstrated. Suitable parameters for this purpose were elucidated and coefficients (weights) for them determined.
A methodologic approach to the comparative study of viruses producing objective data not given by experimental biological studies has been developed. The comparative study is based on the quantitation of similarities of viruses based on integral differences of viruses in all the parameters under study. The results obtained permit us to consider all the viruses as a single system possessing a certain structure which reflects the degrees of similarity and differences between individual virus groups. The analysis of the immediate surroundings of each group determined 5 chains consisting of virus groups situated in the order of their retreat from the group corresponding to the Picornaviridae family. The revealed structure of the virus system allows modelling of evolutionary relations between individual virus groups to be made.
The possibility of using cluster analysis for allocation of viruses into groups having a taxonomic rank below the family was studied. As a result, a modified variant of cluster analysis is proposed which may be used for investigation of similarities and differences among viruses within individual families and formation of groups corresponding to those of a lower taxonomic rank than the family. The use of this modified variant of cluster analysis allowed the authors to distinguish groups in the majority of the families studied corresponding to ICTV genera. The data have been obtained suggesting the necessity of changing the taxonomic rank of some virus groups. The above studies have shown the possibility of developing numerical classification of viruses at the subfamily and genus levels, in other words, a single hierarchical numerical classification of viruses.
The study used the information mass containing information on 83 viruses characterized by 41 markers. The suitability of one of the variants of cluster analysis for virus classification was demonstrated. It was established that certain stages of automatic allotment of viruses into groups by the degree of similarity of their properties end the formation of groups which consist of viruses sufficiently close to each other by their properties and are sufficiently isolated. Comparison of these groups with the classification proposed by the ICVT established their correspondence to individual families. Analysis of the obtained classification system permits sufficiently grounded conclusions to be drawn with regard to the classification position of certain viruses, the classification of which has not yet been completed by the ICVT.
Three methodical approaches were used for reduction of the number of markers necessary for division of viruses into groups corresponding to certain families. Division of the markers into groups characterizing various properties of virions and their components as well as certain stages of virus reproduction in sensitive systems allowed some groups of markers to be excluded without losing the informative value of the marker set. The use of correlationships between markers helped to replace 64 initial parameters with 26 factors. The employment of the method of major components demonstrated the possibility of further reduction of the size of space in which virus clustering is done.