Vol 48, No 4 (2003)

Mucosal viral infections: achievements and problems

Abstract

Data obtained in the recent years on developing the viral inactivated mucosal vaccines by applying the mucosaladhesive adjuvants are presented in the survey. Progress achieved in designing the mucosal influenza vaccines and mucosal vaccines againsta variety of other viral infections is pointed out. Cross-protection against variations of a virus within its subtype limits as well as overcoming of a negative influence of parent antibodies produced ort the immunogenicity of live-vaccines', which were used at young age, were observed in the intranasal administration of viral mucosal vaccines. A number of shortcomings of bacterial toxins used as mucosal-adhesive adjuvants as well as problems, which may arise when the viral mucosal vaccines are used on a large-scale basis due to a need in their two- and-threefold intranasal administration, are in the focus of attention.
Problems of Virology. 2003;48(4):4-
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Spread and properties of epidemic strain of influenza A and В viruses accountable for a morbidity rise in Russia during 1999-2002

Abstract

The strains of influenza A -A(H1N1), A(H3N2) and В viruses were shown in the paper to have been circulating in Russia in 1999-2002. A co-circulation of viruses of 2 to 3 types was detected in all epidemic seasons. A majority of strains was isolated on the culture of cells MDCK. A study of epidemic strains revealed the predominance of ,^-viruses A(H3N2) IFr№99-2000, the predominance of viruses A(h1 N1) in 2000-2001, and the predominance of influenza В viruses in 2001-2002. According to the conducted antigenic analysis, all A(H1 N1) isolates were similar to the etalon A/New Caledonia/20/99. The antigenic drift of hemagglutinin of A(H3N2) epidemic strains was oriented towards the etalons of A/Sydney/5/97 - A/Moscow/10/99; while in influenza В viruses it was oriented towards the etalons B/Beejing/184/93 - B/Yamanashi/166/98 - B/Sichuan/379/99. Sequencing of hemagglutinin gene HA1 showed certain difference in the\gene structure of epidemic strains A(H1N1) and A(H3N2) versus the etalon ones, which were registered, including at antigen sites. An analysis of paired sera obtained from patients confirmed the virologic findings, i.e. it detected a growth of antibodies to viruses that circulated during an actual season.
Problems of Virology. 2003;48(4):11-15
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The immune response in oral and rectal immunization by the attenuated strain of Salmonella carrying the HIV DNA-vaccine

Abstract

The recombinant strain of Salmonella typhimurium SL7207/pBMC-env, carrying a plasmid containing the gene of protein HIV-1 gp-160, was obtained under the monitoring by CMV-promoter. The above strain was used in the rectal and oral immunization of BALB/c mice. HIV-specific antibodies were detected in serum after a one-time immunization; such antibodies were able to inhibit the viral replication in vitro. Furthermore, the shaping-up of the specific cytotoxic and of proliferative responses was registered. Finally, the rectal immunization by cells of the Salmonella recombinant strain can be regarded as a promising delivery system of DNA-vaccine (pBMC-env), and it is more effective versus the oral immunization variant.
Problems of Virology. 2003;48(4):16-20
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A retrospective analysis of population-type variability of region V3gp120 in the HIV-infected patients with a unified infection focus

Abstract

Regions of HIV-1 genome, encoding the V3 gp120 region, were sequenced in materials that were sampled from persons belonging to the category of individuals infected from a single source during the Rostov-Elista outbreak. The samples were obtained in 1991-1992 (10 pieces) and in 2000-2001 (16 pieces), which amounts to 8% and 13%, respectively, of a total number of patients infected by the beginning of 1990. It was established that the level of the population variability of amino-acid sequences in region V3 amounted, in 1991-1992, to 5.2% and increased to 9.1% in the samples of 2000-2001. A comparison ofamino-acid sequences in region V3from the collections of 1991-1992 and of 2000-2001 revealed the below amino-acid substitutions: from Ser13 to His, from Ley 14 to Phe, from Phe to Ley and from Ley to Ala. An analysis of V3 B-epitope showed that the basic trend of its evolution consists in reciprocal transitions of L to F in position 14 and of F to L in position 20. Such substitutions ensure further changes at the "top" of the V3-loop from GPG to APG.
Problems of Virology. 2003;48(4):20-26
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The temperature sensitivity of epidemic influenza A viruses as a possible marker of the immunogenicity of reassortant vaccinal strains

Abstract

The influence of ts-phenotype of epidemic viruses and of cold-adapted (CA) reassortant vaccines' strains, appropriately prepared, produced on the human immunogenicity was under investigation. A widespread variability of epidemic viruses' thermal sensitivity sign was established. It was shown that the CA reassortant vaccine strains, obtained through crossbreeding of attenuation donors and of thermally resistant epidemic viruses, are described by a higher immunogenicity. Therefore, the immunogenicity of live influenza vaccines (LIV) can be defined by the ts-phenotype of epidemic parent viruses, which must be sampled for the reassortant vaccine strains not only through searching for samples of antigenically actual viruses but also through search for non-ts-phenotype viruses.
Problems of Virology. 2003;48(4):26-29
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The comparative analysis of wild measles viruses strains isolated in the European Part of the Russian Federation

Abstract

Eleven wild measles virus isolated, in 1988 and in 1999-2001 in the European territory of the Russian Federation, were investigated. On the basis of an analysis of N-gene region sequences, encoding the COOH terminal end of nucleoprotein, the isolates were divided into 2 subgroups. According to the WHO classification, subgroup 1 was in line with genotype A and subgroup 2 - with genotype D. Subgroup 2 was close to genotype D4 but differed from it according to its composition of nucleotides on the average by 2.8%, and according to its amino-acid composition - by 2.6%. with respect to the WHO criteria, the latter can be referred to prelimarily as an independent genotype. Finally, the measles viruses' strains of genetic groups A and D circulated in the Russian Federation in 1988, and in 1999-2001.
Problems of Virology. 2003;48(4):29-35
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Gliosis as a trigger of pathomorphologies! changes in prion diseases

Abstract

Experiments with three cell lines revealed that the scrapiecontaining cerebral extract, obtained from preliminarily infected 6-month mice, sharply induced the cellular proliferation, which was registered yet in 3 days after incubation. However, the cerebral extract of healthy 6-month mice did not virtually influence the velocity of cells' reproduction in all three cultures. The authors suggest, with respect to published data and to their independently found research results, that the gliosis is of primary importance in shaping up the pathomorphological alterations in the cerebral tissue in prion diseases of man and animal.
Problems of Virology. 2003;48(4):35-37
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Immune-regulating Th1 - and Th-2 cytokines in chronic infections caused by hepatitis В and С viruses

Abstract

The serum levels of Th1 (y-lFN and sIL-2r) and of Th2 (IL-10) cytokines were measured in 33 patients (23 males and 10 females, mean age 23.1 ± 1.9) with chronic viral hepatitis (CVH) according to a disease etiology (6 patients with hepatitis В - CVHB, 15 patients with hepatitis С - CVHC, and 12 patients with a mixed form of chronic hepatitis В and С - HBV + HCV). Besides, the contents of the studied cytokines were compared with the traditional infection markers and the presence of vircmia. The similar indices taken from 10 healthy persons served as controls. The concentration of y-IFN was found to be reliably higher (p < 0.05) in patients of all three groups (0.32 ± 0.07, 0.34 ± 0.09 and 0.25 ± 0.06 pg/ml, respectively) regardless of a disease etiology and as compared with the control value (0.09 ± 0.04) pg/ml). At the same time, the levels of y-IFN, sIL-2r and IL-10 (0.25 ± 0.06 pg/ml, 166.5 ± 31.3 IU/ ml and 48.1 ± 8.4 pg/ml, respectively) was found to be reliably (p < 0.05 and p < 0.01) higher, as compared to the controls (0.09 ± 0.04, 57.1 ± 5.6 and 10.8 ±7.8, respectively), only in patients with the mixed infection of hepatitis. Like in our previous study, a trend was established towards the growing mean values of the IL-r level from its lowest parameters in the group of CVHB patients towards its highest parameters in the group with the mixed hepatitis form. According to our data, the IL-2r level correlated reliably with the activity of AlAt (r = 0.452; p < 0.05), while the yIFN content correlated reliably with the IL-10 concentration (r = 0.805; p < 0.05), and the y-IFN content correlated .with the IL-10 concentration (r = 0.805; p < 0.01) irrespective of disease pathology.
Problems of Virology. 2003;48(4):37-40
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The antiviral activity of the Gepon piptide immunomodulator in experimental models of street rabies virus

Abstract

Intracerebral injections of the Gepon drug were shown to be non-toxic when administered to outbreed white mice, 0.01-0.1 цд. The drug protects 30-40% of mice (p < 95-99%) in contamination by street rabies virus. The animals' protection depends on a dose and drug application scheme. The most pronounced protection was observed in its intramuscular administration, 0.1 цд in the virus locus (infection opening). It should be necessarily pointed out that such pronounced protection (40%; p < 0.01) was noted within the therapeutic scheme of drug administration after virus infected the animals. A new method is described, which is related with evaluating the antiviral drugs' quality, i.e. with registering the dynamics of morbidity and death of infected animals.
Problems of Virology. 2003;48(4):40-44
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An intensification of the antiviral and interferon-gene effects of ridostin (an interferon inducer) by cationic liposomes in vitro and in intranasal administration

Abstract

Combined application of ridostine with catonic liposomes was shown to essentially enhance the interferon-inducing and antiviral activity of the former in experiments with cell cultures L-929, which is apparently related with an improved efficiency of intracellular delivery of dsRNA. A comparative study demonstrated that ridostine, when combined with liposomes, is needed by 103-10* times less as when it is used alone. A pretreatment of the cellular monolayer by cationic liposomes contributes also to enhancing the activity of ridostine, which can be explained by an enhanced permeability of cells for dsRNA holding on-for as long as 30 minutes after the removal of liposomes from the liquid culture. A separate successive administration of, first, liposomes and, then, of ridostine in BALB/c mice (20 mg/kg) leads to a more intensified induction of interferon in the upper respiratory tract tissues as compared with the administration of ridostine alone.
Problems of Virology. 2003;48(4):45-47
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Studies of Far-East encephalitis: historic aspects

Abstract

История советской науки сталинской эпохи полна умолчаний, искажений, прямых фальсификаций, плагиата. Только в последние годы, когда открылся доступ ко многим архивам, когда стали публиковаться документы, воспоминания очевидцев и свидетелей, когда историки стали не подгонять факты на потребу дня, а анализировать их, рухнули многие мифы, выявились поражающие воображение обстоятельства. История отечественной вирусологии - не исключение. В 1937 г. экспедиция по руководством Льва Александровича Зильбера (1894-1966), впоследствии действительного члена АМН СССР, лауреата двух премий - Сталинской (1946) и Государственной (1967), а в то время профессора, руководителя Центральной вирусной лаборатории Наркомздрава РСФСР, заведующего Отделом вирусов Института микробиологии АН СССР, открыла возбудителя и переносчика тяжелейшего заболевания, получившего тогда название дальневосточного весенне-летнего, или клещевого, энцефалита. Работая с мая по август в тайге, участники экспедиции, состоящей в основном из молодых ученых, сумели не только выделить новый вирус, но и доказать, что его переносчик - иксодовый клещ, а не комар, как предполагали многие местные врачи. После возвращения в Москву Л. А. Зильбер и некоторые другие участники экспедиции были арестованы. Статья, содержавшая описание открытия, была опубликована без фамилии Л. А. Зильбера и его сотрудницы А. Д. Шеболбаевой (ЖМЭИ, 1938). В отсутствие Л. А. Зильбера началась долгая история умолчаний и искажения этого выдающегося достижения отечественной вирусологии. Достижения экспедиции Л. А. Зильбера 1937 г. стали приписывать всем трем экспедициям (1937, 1938 и 1939 гг.). Открытие вируса как бы оставалось за Л. А. Зильбером (без упоминания его имени), а открытие переносчика (клеща) "переместилось"к другим ученым. Даже в учебниках для средней школы послевоенного времени история открытия клещевого энцефалита была искажена до неузнаваемости. Понадобилось много лет, прежде чем истина восторжествовала, но даже сейчас, когда в ряде публикаций, в том числе участников экспедиции, все встало на место, иногда пытаются возродить старые мифы. Публикация, которую вы прочтете, касается событий, происходивших в Москве уже после экспедиции Л. А. Зильбера и без его участия. Прошли многие десятки лет, но трагическая гибель сотрудницы Л. А. Зильбера Надежды Вениаминовны Каган не оставит равнодушным и современного читателя. Академик РАН Л. Л. Киселев
Problems of Virology. 2003;48(4):48-48
pages 48-48 views


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