New Pathogenic Viruses of Natural Foci in Primorye Isolated over the 80-Year History of the Institute: A Review of Virological Studies

Background: The discovery of a new viral disease called tick-borne encephalitis (TBE) in the Far East in 1937 triggered the thematic virology research on the Eurasian continent. The purpose of our study was to conduct a virological and epidemiological monitoring of tick-borne viral infections in the Primorsky Krai over an 80-year period. Materials and methods: Several hundreds of strains belonging to the viruses of the TBE complex (Flaviviridae family) and other families have been isolated; their biological, antigenic and molecular genetic characteristics have been studied. Results: The most complete picture of the Far Eastern population of the TBE virus was obtained in the 1990s based on whole genome sequencing of 50 TBEV strains isolated from patients with different clinical manifestations of the disease and from ixodid ticks. It was established that all the strains belong to the same Far Eastern subtype of TBEV with three clusters (Oshima-, Sofjin-, and Senzhang-). In 1972, the Powassan virus was first isolated from Haemaphisalis longicornis ticks on the Eurasian continent. Phylogenetic analysis based on the whole genome characteristics of the Spassk-9, Nadezdinsk-1991 and Partizansk-2006 strains, as well as the characteristics of five fragments of other Powassan virus strains, indicated that they all belong to the Powassan virus lineage I. The first comparative description of three strains Primorye-155-77, Primorye-20-79 and Primorye-185-91 of the Louping ill virus was given. A comprehensive study of the isolated Ozernoe strain of a deceased female patient enabled identification of the first clinical case of the lyssavirus disease in the Asian part of Russia. This strain is genetically close and has a common ancestor with the Irkut strain and is attributed to pathogens of the genus Lyssavirus, family Rhabdoviridae. Conclusion: Isolation of a highly pathogenic lyssavirus and several viruses of the TBE complex indicates the importance of such virology surveillance and proves the necessity of its continuation.

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Tick-borne encephalitis in the Far East focal region of the Eurasian continent

Journal of microbiology epidemiology immunobiology ◽

10.36233/0372-9311-2020-97-2-150-158 ◽

2020 ◽

Vol 97 (2) ◽

pp. 150-158

Author(s):

Galina N. Leonova

Keyword(s):

South Korea ◽

Far East ◽

Tien Shan ◽

Ixodid Ticks ◽

Focal Region ◽

Wild Rodents ◽

Eurasian Continent ◽

Tick Borne Encephalitis ◽

Natural Foci ◽

Far Eastern

The analysis of the activity of natural foci of tick-borne encephalitis (TBE) in the Far Eastern Federal District (Primorsky and Khabarovsk Territories, the Jewish Autonomous and Amur Regions), represented by a single Sikhote-Alin focal region was performed. Endemic territories of China, Korea, Japan are adjacent to this focal region. In the last decade the decrease of the infection rate in ixodid ticks and the morbidity of TBE compared to the 1990s was observed. Data on the infection rates in ixodid ticks based on ELISA, PCR and TBEV isolation are often discrepant. Active circulation of TBEV that involved dominant and less significant species of ixodid ticks and mouse-like rodents has been demonstrated since 1952 in China, since the 1990s in Japan and since 2011 in South Korea. The circulation of TBEV strains of the Far Eastern subtype was determined in all these territories. The exception was 7 strains isolated in South Korea, which appeared to be the European subtype based on the results of molecular genetic analysis. Two new strains of TBEV from the organs of wild rodents Marmota himalayana were isolated in 2017 in the territories of previously unknown natural foci in the Tien Shan, China. The genetic divergence of these strains from three TBEV subtypes allowed us to establish the existance of a new Himalayan TBEV subtype (Him-TBEV), which, according to the authors, has been "hidden" for hundreds of years. One can also speculate the processes of emergence of new TBEV subtypes The most complete picture of the Far Eastern population of TBEV was obtained in the last decade of the twentieth century, which served as the basis and impetus for the study and comparative analysis of the differences in numerous strains of TBEV isolated on the territory of the Eurasian continent.

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Clinical and genetic characteristics of rare pathogenic variants of the CFTR gene in Russian patients with cystic fibrosis

Russian Pulmonology ◽

10.18093/0869-0189-2021-31-2-148-158 ◽

2021 ◽

Vol 31 (2) ◽

pp. 148-158

Author(s):

A. Yu. Voronkova ◽

Yu. L. Melyanovskaya ◽

N. V. Petrova ◽

T. A. Adyan ◽

E. K. Zhekaite ◽

...

Keyword(s):

Cystic Fibrosis ◽

Genetic Variants ◽

Pancreatic Insufficiency ◽

Protein Energy Malnutrition ◽

Molecular Genetic ◽

Clinical Manifestations ◽

Cftr Gene ◽

Genetic Characteristics ◽

Missense Variants ◽

Pathogenic Variants

The variety of clinical manifestations of cystic fibrosis is driven by the diversity of the CFTR gene nucleotide sequence. Descriptions of the clinical manifestations in patients with the newly identified genetic variants are of particular interest.The aim of this study was to describe clinical manifestations of the disease with the newly identified genetic variants.Methods. Data from Registry of patients with cystic fibrosis in the Russian Federation (2018) were used. The data review included three steps — the search for frequent mutations, Sanger sequencing, and the search for extensive rearrangements by MLPA. 38 pathogenic variants were identified that were not previously described in the international CFTR2 database. We selected and analyzed full case histories of 15 patients with 10 of those 38 pathogenic variants: p.Tyr84*, G1047S, 3321delG, c.583delC, CFTRdele13,14del18, CFTRdele19-22, c.2619+1G>A, c.743+2T>A, p.Glu1433Gly, and CFTRdel4-8del10-11.Results. A nonsense variant p.Tyr84* was found in 5 patients (0.08 %). Two missense variants c.3139G>A were found in 2 siblings (0.03 %). The c.4298A>G was found in 1 patient. Other variants were detected in a single patient (0.02 %) each. They included two variants of a deletion with a shift of the reading frame 3321delG and c.583delC, two splicing disorders c.2619+1G>A and c.743+2T>A, three extended rearrangements CFTRdele19-22, CFTRdele13,14del18, and CFTRdel4-8del10-11. The last two variants include 2 rearrangements on one allele, which cause the severe course in two young children. 8 of the 10 variants are accompanied by pancreatic insufficiency (PI). Among patients with p.Tyr84*, one had ABPA, one had liver transplantation, and all had Pseudomonas aeruginosa infection. Nasal polyps were diagnosed in 2 patients with p.Tyr84*, 1 with G1047S, 1 with CFTRdel4-8del10-11, and 1 patient with 3321delG, who also had osteoporosis and cystic fibrosis-related diabetes (CFRD). 2 patients with PI with 3321delG and CFTRdel4-8del10-11 genetic variants, and 1 with PI with p.Glu1433Gly genetic variant had severe protein-energy malnutrition (PEM).Conclusion. Clinical manifestations of previously undescribed CFTR genetic variants were described. 5/10 genetic variants should be attributed to class I, 3/10 – to class 7 of the function classification of pathogenic CFTR gene variants associated with transcription and translation disruptions. Class of the identified missense variants c.3139G>A and c.4298A>G has not been established and requires further functional, cultural, and molecular genetic studies.

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Phylogenetic analysis and distribution of far eastern tick-borne encephalitis virus subtype (Flaviridae, Flavirus, TBEV-FE) from Asia

Voprosy Virusologii ◽

10.36233/0507-4088-2019-64-5-250-256 ◽

2019 ◽

Vol 64 (5) ◽

pp. 250-256 ◽

Cited By ~ 1

Author(s):

G. N. Leonova ◽

S. I. Belikov

Keyword(s):

Molecular Genetic ◽

Primorsky Krai ◽

Khabarovsk Krai ◽

Genetic Characteristics ◽

Tick Borne Encephalitis ◽

Tbe Virus ◽

Tick Borne Encephalitis Virus ◽

Far Eastern ◽

Virus Strains ◽

Virus Subtype

To date, a lot of data on molecular genetic characteristics of different tick-borne encephalitis virus strains has appeared. Only on the basis of the E protein genome, sequences of about 1,500 TBEV strains were registered in GenBank.The purpose of the work – revision and comparative analysis of data on complete genomes sequences of the Far Eastern subtype of TBE virus strains distributed in the Asian part of Eurasian continent.Material and methods. The data on the complete genomes of 84 strains of TBEV isolated in Asia were used; phylogenetic analysis was performed.Results and discussion: it was shown that variants of the TBEV of the Far Eastern subtype are circulating here and form three separate clusters (Sofjin, Senzhang- и Shkotovo-like strains). Sofjin strain (Sofjin-1953, Sofjin-Chumakov, Sofjin-KSY) was considered to be the reference for Far Eastern TBE virus subtype strains and a cluster of Sofjin-like strains. Sofjin-like strains were not found in China and Japan, but widely distributed throughout the area of Primorsky and Khabarovsk krai. The group of Senzhang-like strains was distributed in China, Eastern Siberia, Khabarovsk krai and northern Primorsky krai, but was not found in Japan (Hokkaido). According to molecular genetic characteristics the youngest and more genetically homogeneous group was the Shkotovo-like strains, isolated in the southern part of Primorsky krai, however not found on Hokkaido Island (Japan).Conclusion: revision of the complete genome characteristics of TBEV strains revealed the features of micro-evolutionary process of viral populations in the Asian part of Eurasia, show the individual affection of strains to certain territories, as well as detect random finds of such strains in the territories of other natural foci.

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MOLECULAR-GENETIC CHARACTERISTICS OF THE COXSAKIE A10 ENTEROVIRUS THAT WAS CIRCULATING IN THE CONSTITUENT ENTITIES OF THE RUSSIAN FAR EAST

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-2018-4-3.39 ◽

2019 ◽

Vol 8 (4) ◽

pp. 534-535

Author(s):

E. Yu. Sapega ◽

L. V. Butakova ◽

O. E. Trotsenko

Keyword(s):

Russian Far East ◽

Molecular Genetic ◽

Far East ◽

Genetic Characteristics ◽

The Russian Far East

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Clinical and genetic characteristics of ponto-cerebellar hypoplasia caused by mutations in the TSEN54 gene (OMIM: 277470)

Neuromuscular Diseases ◽

10.17650/2222-8721-2019-9-2-30-36 ◽

2019 ◽

Vol 9 (2) ◽

pp. 30-36

Author(s):

E. I. Dadali ◽

I. A. Akimova ◽

N. A. Semenova ◽

D. M. Guseva ◽

O. A. Shchagina ◽

...

Keyword(s):

Molecular Genetic ◽

Genetic Diagnosis ◽

Clinical Manifestations ◽

Compound Heterozygous ◽

Pontocerebellar Hypoplasia ◽

Genetic Characteristics ◽

Molecular Genetic Diagnosis ◽

Severity Of The Disease ◽

Detection Of Mutations ◽

Compound Heterozygous State

Introduction. The description of the clinical and genetic characteristics of eight patients with autosomal-recessive variant pontocerebellar hypoplasia due to mutations in the TSEN54 gene.Purpose. Description of clinical and genetic characteristics of Russian patients with type 2A and type 4 of pontocerebellar hypoplasia.Materials and methods. The diagnosis of pontocerebellar hypoplasia was established on the basis of the specific features of clinical manifestations and detection of mutations in the gene TSEN54 based on the analysis of the results of exome sequencing. Results. 8 patients with pontocerebellar hypoplasia caused by mutations in the TSEN54 gene were identified. Discussion. Based on the features of clinical manifestations and severity of the disease in 5 patients diagnosed pontocerebellar hypoplasia type 2A, and in 3 patients – type 4. In patients with type 2A of pontocerebellar hypoplasia discovered mutation c. 919G>T (p.Ala307Ser) in a homozygous state. Patients with type 4 of pontocerebellar hypoplasia this mutation is detected in the compound heterozygous state with c.670_671delAA (p.Lys224fs) and c.1264C>T (p.Gln422fs).Conclusion. The obtained results allow us to conclude that, as well as in European populations, the mutation c.919G>T (p. Ala307Ser) is a major in Russian patients with pontocerebellar hypoplasia 2A and 4 types, which account for about half of all cases of this disease group. The search for this mutation should be the first stage of molecular genetic diagnosis in patients with clinical and magnetic resonance signs of pontocerebellar hypoplasia.

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MOLECULAR GENETIC CHARACTERISTICS OF HIV-1 VARIANTS ISOLATED IN THE SUBJECTS OF THE RUSSIAN FAR EAST

Voprosy Virusologii ◽

10.18821/0507-4088-2019-64-2-79-89 ◽

2019 ◽

Vol 64 (2) ◽

pp. 79-89

Author(s):

V. O. Kotova ◽

O. E. Trotsenko ◽

L. A. Balakhontseva ◽

E. A. Bazykina

Keyword(s):

Genetic Variants ◽

Russian Far East ◽

Molecular Genetic ◽

Far East ◽

Federal District ◽

Genetic Monitoring ◽

Hiv Positive ◽

Far Eastern ◽

Hiv 1 ◽

The Russian Far East

Introduction. Molecular-genetic monitoring of human immunodeficiency virus (HIV) drug-resistant strains circulation as well as analysis of territorial peculiarities of different genetic variants prevalence of the virus is a crucial part of epidemiological surveillance over HIV-infection spread. Objective of the research - to analyze the prevalence of HIV-1 genetic variants among HIV-positive people living in different constituent entities of the Far Eastern Federal District. Material and methods. Molecular-genetic analysis of the Pol-gene that is coding protease and a part of reverse transcriptase of HIV-1 was performed for a total number of 206 blood plasma samples. The biological material was collected from HIV-positive people living in Sakhalin, Magadan and Amur regions, Jewish Autonomous District, Khabarovsk region, Republic of Sakha (Yakutia) and Chukotka Autonomous Region (constituent entities of the Russian Federation in the Russian Far East). Results. The research demonstrated that HIV-1 sub-subtype A6 continues to be dominant and comprises 72.1±3.1% of all isolated subtypes in the regions of the Russian Far East. HIV-1 subtype B was identified in 14 cases (6.8±1.8%) and subtype C in 4 cases (1.9±1.0%). Spectrum of HIV-1 recombinant forms was determined for some regions. We identified five types of HIV-1 circulating recombinant forms (CRF): CRF03_AB - 2 (0.9±0.7%), CRF02_AG - 8 (3.9±1.3%), CRF63_02A1 - 27 (13.1±2.4%), CRF11_cpx - 1 (0.5±0.5%), CRF01_AE - 3 (1.5±0.8%). High heterogeneity of the virus was registered in the Jewish Autonomous District. Discussion. The conducted research revealed genetic differences in the landscape of HIV-1 subtypes circulation as well as differences in HIV-1 recombinant forms distribution frequency in the Russian Far East. Current findings are due to expansion of migration flows that promote cross-border importation and further spread of different HIV-1 genetic variants among population of the Far Eastern Federal District. Conclusion. The conducted research revealed that the molecular-genetic monitoring of HIV-1 genovariants should involve not only regions with high HIV-abundance but also with low HIV-prevalence and incidence.

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Clinical Manifestations and Bacterial Genomic Analysis of Group A Streptococcus Strains That Cause Pediatric Toxic Shock Syndrome

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piy069 ◽

2018 ◽

Vol 8 (3) ◽

pp. 265-268

Author(s):

Roman Deniskin ◽

Brittany Shah ◽

Flor M Muñoz ◽

Anthony R Flores

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Toxic Shock Syndrome ◽

Group A Streptococcus ◽

Clinical Manifestations ◽

Streptococcal Toxic Shock Syndrome ◽

Whole Genome ◽

Toxic Shock ◽

Genetic Characteristics ◽

Group A

Abstract We report here 18 cases of pediatric group A streptococcal toxic shock syndrome, associated clinical findings, and bacterial molecular genetic characteristics discovered through whole-genome sequencing. This comparative whole-genome sequencing revealed unique gene content (speK) and polymorphisms (dpiB) in emm87 group A Streptococcus, the relative contributions of which, in combination with the host response, in the development of streptococcal toxic shock syndrome remain to be elucidated.

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Tick-borne encephalitis virus – a review of an emerging zoonosis

Journal of General Virology ◽

10.1099/vir.0.011437-0 ◽

2009 ◽

Vol 90 (8) ◽

pp. 1781-1794 ◽

Cited By ~ 269

Author(s):

K. L. Mansfield ◽

N. Johnson ◽

L. P. Phipps ◽

J. R. Stephenson ◽

A. R. Fooks ◽

...

Keyword(s):

Clinical Manifestations ◽

Northern China ◽

Encephalitis Virus ◽

Ixodid Ticks ◽

Ixodes Persulcatus ◽

Tick Borne Encephalitis ◽

Far Eastern Russia ◽

Tick Borne Encephalitis Virus ◽

Far Eastern

During the last 30 years, there has been a continued increase in human cases of tick-borne encephalitis (TBE) in Europe, a disease caused by tick-borne encephalitis virus (TBEV). TBEV is endemic in an area ranging from northern China and Japan, through far-eastern Russia to Europe, and is maintained in cycles involving Ixodid ticks (Ixodes ricinus and Ixodes persulcatus) and wild vertebrate hosts. The virus causes a potentially fatal neurological infection, with thousands of cases reported annually throughout Europe. TBE has a significant mortality rate depending upon the strain of virus or may cause long-term neurological/neuropsychiatric sequelae in people affected. In this review, we comprehensively reviewed TBEV, its epidemiology and pathogenesis, the clinical manifestations of TBE, along with vaccination and prevention. We also discuss the factors which may have influenced an apparent increase in the number of reported human cases each year, despite the availability of effective vaccines.

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GCK-MODY diabetes course in persons over 18 years of age: prospective observation

Diabetes Mellitus ◽

10.14341/dm12319 ◽

2021 ◽

Vol 24 (2) ◽

pp. 133-140

Author(s):

A. K. Ovsyannikova ◽

E. V. Shakhtshneider ◽

D. E. Ivanoshchuk ◽

M. I. Voevoda ◽

O. D. Rymar

Keyword(s):

Carbohydrate Metabolism ◽

Molecular Genetic ◽

Young Patients ◽

Clinical Manifestations ◽

Oral Glucose ◽

Genetic Characteristics ◽

Glucose Lowering ◽

Target Values ◽

Dipeptidyl Peptidase 4 Inhibitors

Most young patients with hyperglycemia have type 1 diabetes and type 2 diabetes but up to 10% of all cases of the disease occur in MODY (Maturity Onset Diabetes of the Young). Published abstracts show features of the debut, laboratory and genetic characteristics of MODY in the Russian population. However there is a small amount of data on the clinical course of this nosology in the Russian Federation.Aim: To investigate the characteristics of the 3-year course of GCK-MODY diagnosed after 18 years.Materials and methods: 85 probands and 46 relatives of the first and second degrees of kinship with a clinical diagnosis of GCK-MODY were examined: biochemical and hormonal blood tests, ultrasound, molecular genetic studies. Patients were invited for a follow-up visit 3 years after verification of the pathogenic mutations associated with GCK-MODY. Examination, biochemical and hormonalanalyzes , ultrasound were done in second visit.Results: The diagnosis GCK-MODY was verified by a molecular genetic study in 25 probands (29.4%). In 33 of 46 (71.7%) relatives of patients with GCK-MODY were diagnosed identical mutations. In 31 patients with GCK-MODY diagnosed after 18 years, a dynamic observation was performed for three years. Most patients over 18 years of age did not have clinical manifestations of carbohydrate metabolism disorders when diagnosing GCK-MODY and follow up visit. Skin rashes and allergic reactions prevailed among concomitant pathologies. Patients with GCK-MODY had preserved β-cell secretion, HbA1c targets were achieved. Low fasting hyperglycemia prevailed which persisted even after treatment correction. Among the characteristics of carbohydrate metabolism, biochemical, lipid and hormonal parameters during GCK-MODY verification and after three years of observation no significant differences were obtained, which indicates a stable course of the disease. Half of the patients achieved normoglycemia by rational nutrition, two people with GCK-MODY within three years after determining the diagnosis were transferred from insulin therapy to oral glucose-lowering drugs. Among oral glucose-lowering drugs prior to GCK-MODY verification most patients used metformin, 3 years later — dipeptidyl peptidase-4 inhibitors.Conclusion. The results of a three-year follow-up of a group of patients with GCK-MODY demonstrate a non-progressive course of this type of diabetes with stable indicators of carbohydrate metabolism and low fasting hyperglycemia that persists after 3 years of observation. With the verification of GCK-MODY and the achievement of the target values of glycated hemoglobin and postprandial glycaemia by rational nutrition, even if a low level of fasting hyperglycemia is determined, the prescription of oral glucose-lowering drugs is not indicated in most cases.

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