Vol 49, No 1 (2003)

A correlation between the detection of proteins and an activity of the pathological process was analyzed in a study of the content of the С virus hepatitis (CVH) proteins in hepatic cells of patients with chronic С hepatitis (CCH). The expression of CVH proteins in frozen sections of biopsy samples of 69 CCH patients was evaluated by using the immune-histological method involving original monoclonal antibodies (MCA) to 5 CVH proteins. The results of the detection of proteins in patients were compared with an activity and stage of CCH (by using histological tests and a level of alanine aminotransferase - AAT). A set of the CVH proteins were found in the liver of 74% of patients, i.e. core proteins, NS3, NS4A, NS4B and NS5A - in 28, 43,43, 55 and 58%, respectively. All studied proteins were detected in the cytoplasm of hepatocytes. Proteins were found in the liver more often as compared with the detection rate of CVH RNA in the blood serum (61%). This demonstrates a high sensitivity of the discussed test at detecting the CVH infection. The accumulation of the core protein was shown to correlate with the presence of the replicative form of CVH RNA in the liver and with a higher level of AAT. The quantity of NS5 A-expressing cells correlated directly with a CCH stage. The quantity of NSB- and NS3-positive hepatocytes correlated negatively with an activity of the infiammotary-and-necrotic processes in the liver. Hyper-fermentation was found more often among the antigen-positive patients. The CCH histological activity was proven to be reliably higher at a simultaneous detection of CCH proteins in the liver and of CVH RNA - in the serum.

An experiment with BALB/c mice, infected with a lethal dosage of the virus of tick-borne encephalitis (ТЕ), strain 205, was accompanied by pronounced growing concentrations of the IL-1 p, IL-6, IL-10 and TNF a cytokines in the blood serum of animals. The maximum values of the above cytokines were determined at the infection terminal stage. A reliably less pronounced growth of concentrations of IL-1 p, TNF a and IL-10 was found in animals infected with a non-lethal ТЕ dosage. The concentration of IL-6 in the blood serum of animals, infected with a non-lethal dosage of the virus, changed during the whole observation period. The dynamics of cytokines in the blood scrum of mice, infected with a lethal dosage of the ТЕ virus, suggests the development of SIRS at the infection terminal stage.

The method of enzyme-linked immunosorbent assay (ELISA) was used to show an interaction of soluble recombinant CD4-receptor (rsCD4) with human apolipoprotein A-1. Competitive interactions between envelope proteins VIH-1 (gp120 and gp41), on the one hand, and human apolipoprotein A-1 with CD4 receptor, present in the cellular membranes of line MT4 human lymphocytes, were demonstrated by the method of flow cytofluorimetry. It was suggested that the competitive interactions between the above proteins could manifest in respect to the apolipoprotein A-1 receptor, which affects the involvement of the latter in the regulation of protein biosynthesis and which leads to a decrease in the body weight of HIV-infected patients.

Electrone-microscopic investigations are indicative of that the cultures of healthy donors, stimulated by phytohemagglutinin (PHA), can be successfully used to study the etiology of parenterally transmitted hepatitis. An electronic-microscopic study of a virus, isolated from the blood serum of a patient with hepatitis on the basis of the PHA-stimulated human leukocyte cultures and named a hepatitis leukocytic virus (HLV), enabled, by using the negative contrasting method, to detect viral particles of the hexagonal shape, sized 50-65 nm, with a coating divided by a 4-5 nm light space. Therefore, the HLV was described as belonging to the Flaviviridae family. RNA of the С hepatitis virus was detected in the К HLV strain stored, for 24 years, at the Museum of the Viruses Research Institute, Russian Academy of Medical Sciences, in a lyophilizated bed at -5 °C, however, an attempt to genotype the RNA failed. No RNA donor leukocytes were found in the materials of further passing of HLV by using the PHAstimuiated cultures, which can be explained by an inactivation of HLV at storage. No RNA of the С hepatitis virus was found in the above materials either, however, in 1999, DNA of the TT virus was detected at passing the strain, which indicates that the virus is widely spread in the population of healthy donors, whose lymphocytes are used preparing the blood leukocyte cultures.

Effect of y-L-glutamy Ihistamine y-L-Glu-HA and some of its derivatives on the state of nonspecific resistance and antiviral activity was studied using experimental models of influenza virus and herpes simplex virus infections. Activities of natural killer (NK) cells and interferon (IFN) system were measured. The model of physical-emotional stress in mice was used. It was shown that the gamma-L-Glu-HA derivative II can prevent totally or substantially a decrease in the NK activity. This agent also prevents inhibition of synthesis of alpha- and gamma-IFN during the post-stress period. The y-L-Glu-HA derivatives II, III, and VII increased the mice resistance to influenza virus type A/Aichi at low infection dose (10LD50). The derivative II showed its protective effect even at high dose of pathogen (100LD50). However, this y-L-Glu-HA derivative was virtually ineffective under harsh experimental conditions. Thus, a number of gamma-L-Glu-HA derivatives tested in this work demonstrated immunomodulation activity. These agents were able to normalize parameters of nonspecific immunity. They exerted a pronounced antiviral effect against influenza virus but were virtually ineffective against encephalitis in mice caused by herpes simplex virus, type 1. Of all tested agents, gamma-L-Glu-HA derivative II was found to be the most promising.

Comprehensive examinations of the population, sanguivorous arthropoda and domestic animals were for the first time held in the territory of the Ulyanovsk region. An active circulation of certain arboviruses was detected and a predominantly ecological relation of California encephalitis serogroup viruses with Aedes mosquitoes, on the one hand, and of Batai viruses with Anopheles mosquitoes, on the other hand, was established. The most reliable detection of antibodies to California encephalitis viral complex was pointed out.