N V Tikunova

Institute of Chemical Biology and Fundamental Medicine, Novo-Nikolaevsk, Novosibirsk, Russia

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Publications (126)132.82 Total impact

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    ABSTRACT: Rotaviruses C (RVC) cause sporadic cases and outbreaks of diarrhea in humans and animals worldwide. The aim of this study was to monitor RVC during a surveillance study of sporadic cases of viral gastroenteritis in the Novosibirsk and Omsk regions of Russia from 2006 to 2011. A total of 2144 stool samples from children and adults hospitalized with acute gastroenteritis were tested for RVC by RT-PCR. Sixteen RVC-positive stool samples were detected at a rate of 0.6% (13/2037) in children and 2.8% (3/107) in adults. The low detection rate suggested that RVC infection was an uncommon cause of hospitalization in Russia. The complete VP7, VP4, VP6, and NSP4 gene sequences were determined. It was found that RVCs with at least two different genome backgrounds circulated in Siberia. VP4, VP6, and NSP4 gene sequences of most Russian RVC strains clustered with South Asian strains, while the VP7 gene showed a closer relationship to European strains. Meanwhile, only VP4 and NSP4 sequences of the strain Omsk08-386 clustered with South Asian strains, while its VP6 and VP7 sequences clustered with European strains. This is the first genetic characterization of Russian RVC strains and the first report on the prevalence of RVC in the Asian part of Russia.
    Full-text · Article · Apr 2016 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: We investigated whether levels and repertoires of anti-interleukin-18 (IL-18) autoantibodies (auto-Abs) differ in multiple sclerosis (MS) patients and healthy donors (HDs). IL-18 concentration in MS patients' sera was higher than in HD, but the level of anti-IL-18 auto-Abs was lower in MS patients. Correlation patterns of IL-18/anti-IL-18 auto-Abs system differed in HD and MS patients, so we have compared segment composition of the anti-IL-18 single-chain variable fragments (scFvs) selected from MS and naïve phage display libraries. Considerable differences between anti-IL-18 auto-Abs of these libraries were found. MS panel contained auto-Abs displaying both signs of "fetal" and somatically hypermutated repertoires. Naïve panel mainly contained the naïve antibodies. These variations from the norm are possible results of abnormal regulation of the repertoire perhaps determined by remodeling of the molecular mechanisms involved in the V(D)J recombination and/or abnormal selection by antigen in MS pathogenesis.
    No preview · Article · Jan 2016 · Immunogenetics
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    Full-text · Dataset · Jan 2016
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    ABSTRACT: Human bocavirus (HBoV) can cause respiratory diseases and is detectable in the stool samples of patients with gastroenteritis. To assess the prevalence of HBoV in children hospitalized with acute gastroenteritis in Novosibirsk, Russia, as well as its genetic diversity and the potential role in the etiology of gastroenteritis in this region, a total of 5502 stool samples from children hospitalized with gastroenteritis from 2010 to 2012, n=5250, and healthy children, n=252, were assayed for the presence of HBoV DNA by semi-nested PCR. The HBoV DNA was found in 1.2% of stool samples from children, with gastroenteritis varying from 0.5% in 2012 to 1.7% in 2011. The prevalence of HBoV in healthy children was 0.3%. HBoV strains were detected throughout the year with an increase in the fall-winter season. In 87% of cases, HBoV was detected in children before 1year of age. All known HBoV genetic variants have been detected in Novosibirsk, although with different prevalence: HBoV2>HBoV1>HBoV4>HBoV3. At the beginning of 2011, HBoV2 replaced HBoV1 as the most prevalent variant. The median age of children with detected HBoV1 was 8.3months, and that with HBoV2 was 8.0months. All HBoV-positive samples were assayed for the presence of the rotaviruses A and C, norovirus GII, astrovirus, enterovirus, adenovirus F, Salmonella spp., Campylobacter spp., Shigella spp., and EIEC. HBoV1 and HBoV2 as single agents were found in 45.8% and 60% samples, respectively, although this difference was not statistically significant. In the case of co-infections, HBoV was most frequently recorded with rotavirus A and norovirus GII. This study demonstrated that the detection rate of HBoV in stool samples from children with gastroenteritis was low, although both HBoV1 and HBoV2 could be found as the sole agents in children with gastroenteritis in Novosibirsk.
    Full-text · Article · Jan 2016 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    Full-text · Dataset · Oct 2015
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    ABSTRACT: The majority of human group A rotaviruses possess the P[8] VP4 genotype. Recently, a genetically distinct subtype of the P[8] genotype, also known as OP354-like P[8] or lineage P[8]-4, emerged in several countries. However, it is unclear for how long the OP354-like P[8] gene has been circulating in humans and how it has spread. In a global collaborative effort 98 (near-)complete OP354-like P[8] VP4 sequences were obtained and used for phylogeographic analysis to determine the viral migration patterns. During the sampling period, 1988-2012, we found that South and East Asia acted as a source from which strains with the OP354-like P[8] gene were seeded to Africa, Europe, and North America. The time to the most recent common ancestor (TMRCA) of all OP354-like P[8] genes was estimated at 1987. However, most OP354-like P[8] strains were found in three main clusters with TMRCAs estimated between 1996 and 2001. The VP7 gene segment of OP354-like P[8] strains showed evidence of frequent reassortment, even in localized epidemics, suggesting that OP354-like P[8] genes behave in a similar manner on the evolutionary level as other P[8] subtypes. The results of this study suggest that OP354-like P[8] strains have been able to disperse globally in a relatively short time period. This, in combination with a relatively large genetic distance to other P[8] subtypes, might result in a lower vaccine effectiveness, underscoring the need for a continued surveillance of OP354-like P[8] strains, especially in countries where rotavirus vaccination programs are in place.
    No preview · Article · Aug 2015 · Molecular Biology and Evolution
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    Full-text · Dataset · Jul 2015
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    ABSTRACT: Polycyclic aromatic hydrocarbons (PAHs) are widely distributed and relocated in the environment as a result of the incomplete combustion of organic matter. Many PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to microorganisms as well as to higher systems including humans. BP is one of the most toxicologically active PAHs and is often used as a prototype for this entire class of contaminants. In order to select anti-BP antibodies, the conjugate of BP with BSA (BP-BSA) was used to screen naïve combinatorial phage library of human scFvs. Seven unique scFvs against BP-BSA were selected after three rounds of selection. Analysis of the genes encoding the scFvs subdivided them to gene families and subfamilies. Homology with the closest germline ranged from 80.21% to 97.57% for heavy chains and 88.89% to 98.57% for the light chains. Four of the seven scFv amino acid residues sequences without stop codons in frame were selected for proteomic analysis with each other. Four scFvs encoded unique non-related proteins with low-sequence identity among them. All CDRs and the boundaries in the CDR3 formation were carried out. Two of the scFvs (T68 and T72) with the highest binding capabilities to PAHs were expressed in E. coli and purified using a nickel resin. The KDs of T68 to BP-BSA, chrysene, pyrene, and benzo[a]anthracene were almost similar, approximately 10−7 M. The KDs of T72 to benzo[a]anthracene and chrysene were 9.42 × 10−8 M and 2.63 × 10−7 M, respectively. The computational models of T68 and T72 active centers were different.
    No preview · Article · Jul 2015 · Immunological Investigations
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    ABSTRACT: The most epidemiologically significant tick species in Siberia involved in transmission of a large number of pathogens causing human infectious diseases is Ixodes persulcatus. Ixodes pavlovskyi, being more active, also poses epidemiological threats. These tick species share morphology, activity seasons and geographic distribution range. In this paper, we characterize the geographic and genetic structures of I. persulcatus and I. pavlovskyi populations inhabiting the southern part of Western Siberia (Russia and Kazakhstan)-the western part of I. pavlovskyi distribution range. The data are based on six distinct Ixodes tick populations. Analysis of the concatenated mitochondrial marker sequences (16S rRNA and COI) and the nuclear sequence (ITS2) showed genetic polymorphisms in both I. persulcatus and I. pavlovskyi ticks inhabiting the sympatric zone. We could not determine the phylogeographic structure of I. pavlovskyi populations whereas for I. persulcatus significant within-region variance was shown. Notably, the abundance of I. persulcatus ticks negatively correlates with nucleotide and haplotype diversity in the concatenated sequence of mitochondrial gene (16S rRNA and COI) fragments. This is the first description of the genetic polymorphism of I. persulcatus and I. pavlovskyi ticks coexisting in a sympatric zone based on analysis of mitochondrial and nuclear markers.
    Full-text · Article · Jul 2015 · Experimental and Applied Acarology
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    ABSTRACT: Rickettsia spp. are the causative agents of a number of diseases in humans. These bacteria are transmitted by arthropods, including ixodid ticks. DNA of several Rickettsia spp. was identified in Ixodes persulcatus ticks, however, the association of Ixodes trianguliceps ticks with Rickettsia spp. is unknown. In our study, blood samples of small mammals (n=108), unfed adult I. persulcatus ticks (n=136), and I. persulcatus (n=12) and I. trianguliceps (n=34) ticks feeding on voles were collected in two I. persulcatus/I. trianguliceps sympatric areas in Western Siberia. Using nested PCR, ticks and blood samples were studied for the presence of Rickettsia spp. Three distinct Rickettsia species were found in ticks, but no Rickettsia species were found in the blood of examined voles. Candidatus Rickettsia tarasevichiae DNA was detected in 89.7% of unfed I. persulcatus, 91.7% of engorged I. persulcatus and 14.7% of I. trianguliceps ticks. Rickettsia helvetica DNA was detected in 5.9% of I. trianguliceps ticks. In addition, a new Rickettsia genetic variant was found in 32.4% of I. trianguliceps ticks. Sequence analysis of the 16S rRNA, gltA, ompA, оmpB and sca4 genes was performed and, in accordance with genetic criteria, a new Rickettsia genetic variant was classified as a new Candidatus Rickettsia species. We propose to name this species Candidatus Rickettsia uralica, according to the territory where this species was initially identified. Candidatus Rickettsia uralica was found to belong to the spotted fever group. The data obtained in this study leads us to propose that Candidatus Rickettsia uralica is associated with I. trianguliceps ticks. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: Ixodes persulcatus, Ixodes pavlovskyi, and Dermacentor reticulatus ticks inhabiting Western Siberia are responsible for the transmission of a number of etiological agents that cause human and animal tick-borne diseases. Because these ticks are abundant in the suburbs of large cities, agricultural areas, and popular tourist sites and frequently attack people and livestock, data regarding the microbiomes of these organisms are required. Using metagenomic 16S profiling, we evaluate bacterial communities associated with I. persulcatus, I. pavlovskyi, and D. reticulatus ticks collected from the Novosibirsk region of Russia. A total of 1214 ticks were used for this study. DNA extracted from the ticks was pooled according to tick species and sex. Sequencing of the V3-V5 domains of 16S rRNA genes was performed using the Illumina Miseq platform. The following bacterial genera were prevalent in the examined communities: Acinetobacter (all three tick species), Rickettsia (I. persulcatus and D. reticulatus) and Francisella (D. reticulatus). B. burgdorferi sensu lato and B. miyamotoi sequences were detected in I. persulcatus and I. pavlovskyi but not in D. reticulatus ticks. The pooled samples of all tick species studied contained bacteria from the Anaplasmataceae family, although their occurrence was low. DNA from A. phagocytophilum and Candidatus Neoehrlichia mikurensis was first observed in I. pavlovskyi ticks. Significant inter-species differences in the number of bacterial taxa as well as intra-species diversity related to tick sex were observed. The bacterial communities associated with the I. pavlovskyi ticks displayed a higher biodiversity compared with those of the I. persulcatus and D. reticulatus ticks. Bacterial community structure was also diverse across the studied tick species, as shown by permutational analysis of variance using the Bray-Curtis dissimilarity metric (p = 0.002). Between-sex variation was confirmed by PERMANOVA testing in I. persulcatus (p = 0.042) and I. pavlovskyi (p = 0.042) ticks. Our study indicated that 16S metagenomic profiling could be used for rapid assessment of the occurrence of medically important bacteria in tick populations inhabiting different natural biotopes and therefore the epidemic danger of studied foci.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: Recently, a new Ehrlichia genetic variant, Ehrlichia sp. Khabarovsk, was identified in tissue samples of small mammals captured in the Russian Far East. To further characterize Ehrlichia sp. Khabarovsk, tissue homogenate from a naturally infected gray red-backed vole (Myodes rufocanus) was passaged three times in newborn laboratory mice. Using nested PCR Ehrlichia sp. Khabarovsk DNA was detected in tissue samples from infected mice at 1-4 weeks post inoculation. Electron microscopic examination revealed morulae containing gram-negative bacterial cells in monocytes of mouse spleen and liver. The size and ultrastructure of these cells corresponded to those described previously and allowed us to identify the bacteria as Ehrlichia sp. The comparison of ehrlichial 16S rRNA, groEL and gltA genes and putative GroEL and GltA amino acid sequences has demonstrated that Ehrlichia sp. Khabarovsk, like Ehrlichia ruminantium, is more distant from all other Ehrlichia species than these species are between themselves. Phylogenetic analysis has shown that Ehrlichia sp. Khabarovsk belongs to the clade formed by Ehrlichia spp. but clusters separately from other Ehrlichia species and genetic variants. These data indicate that Ehrlichia sp. Khabarovsk can be considered as a new candidate species. We propose to designate it as 'Candidatus Ehrlichia khabarensis' according to the territory where this species was found. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · Jun 2015 · Ticks and Tick-borne Diseases
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    ABSTRACT: Noroviruses (NoVs) are an important cause of acute gastroenteritis worldwide. To monitor the molecular epidemiology of NoVs genogroup II (GII) in Novosibirsk, Russia, a total of 10,198 stool samples from young children hospitalized with acute gastroenteritis and two asymptomatic comparison groups were collected from 2003 to 2012. All samples were screened for the presence of NoV GII, rotavirus, and astrovirus by RT-PCR. The prevalence of NoV in gastroenteritis cases was 13.1%, varying from 7.1% to 21.3% in different seasons. Rotavirus and/or astrovirus were detectable in 25% of the NoV-positive samples. NoV was detected throughout the year with a seasonal increase during winter months. Based on sequence analysis of regions D and/or C within the VP1 gene, 892 identified NoV strains were divided into nine genotypes-GII.3 (51%), GII.4 (44%), GII.6 (2%), as well as GII.1, GII.2, GII.5, GII.7, GII.16, and GII.21 (totally, 3%). The prevalence of NoV in the comparison groups was considerably lower (∼2.5%); only GII.4 (n = 6), GII.21 (n = 2) and GII.1 (n = 1) genotypes were revealed. Based on phylogenetic analysis of the ORF1/ORF2 junction region sequences, GII.P21/GII.3 recombinant and GII.P4/GII.4 were prevalent genotypes (totally, 93%) and their ratio changed every season. The median age of children with NoV infection was 6.6 months (range, <1-35 months), but it was different depending on NoV genotype. Children infected with the NoV GII.3 were younger (median 6.2 months) than GII.4-positive patients (median 9.1 months). This is the first long-term systematic study of NoV molecular epidemiology in Russia. J. Med. Virol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · May 2015 · Journal of Medical Virology
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    ABSTRACT: To facilitate the detection of the tick-borne encephalitis virus (TBEV), the causative agent of one of the most severe human neuroinfections, we have developed an immunoassay based on bioluminescent hybrid protein 14D5a-Rm7 as a detection probe. The protein containing Renilla luciferase as a reporter and a single-chain variable fragment (scFv) of murine immunoglobulin to TBEV as a recognition element was constructed, produced by bacterial expression, purified, and tested. Both domains were shown to reveal their specific biological properties-affinity to the target antigen and bioluminescent activity. Hybrid protein was applied as a label for solid-phase immunoassay of the antigens, associated with the tick-borne encephalitis virus (native glycoprotein E or extracts of the infected strain of lab ticks). The assay demonstrates high sensitivity (0.056 ng of glycoprotein E; 10(4)-10(5) virus particles or 0.1 pg virions) and simplicity and is competitive with conventional methods for detection of TBEV.
    Full-text · Article · Apr 2015 · Analytical and Bioanalytical Chemistry
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    ABSTRACT: The majority of human group A rotaviruses possess the P[8] VP4 genotype. Recently, a genetically distinct subtype of the P[8] genotype, also known as OP354-like P[8] or lineage P[8]-4, emerged in several countries. However, it is unclear for how long the OP354-like P[8] gene has been circulating in humans and how it has spread. In a global collaborative effort 98 (near-)complete OP354-like P[8] VP4 sequences were obtained and used for phylogeographic analysis to determine the viral migration patterns. During the sampling period, 1988-2012, we found that South and East Asia acted as a source from which strains with the OP354-like P[8] gene were seeded to Africa, Europe and North America. The time to the most recent common ancestor (TMRCA) of all OP354-like P[8] genes was estimated at 1987. However, most OP354-like P[8] strains were found in three main clusters with TMRCAs estimated between 1996 and 2001. The VP7 gene segment of OP354-like P[8] strains showed evidence of frequent reassortment, even in localized epidemics, suggesting that OP354-like P[8] genes behave in a similar manner on the evolutionary level as other P[8] subtypes. The results of this study suggest that OP354-like P[8] strains have been able to disperse globally in a relatively short time period. This, in combination with a relatively large genetic distance to other P[8] subtypes, might result in a lower vaccine effectiveness, underscoring the need for a continued surveillance of OP354-like P[8] strains, especially in countries where rotavirus vaccination programs are in place.
    No preview · Article · Apr 2015 · Molecular Biology and Evolution

  • No preview · Article · Apr 2015 · Molecular Biology and Evolution
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    ABSTRACT: There was a retrospective analysis of the detection of viral and bacterial pathogens of acute gastroenteritis in more than 3,000 young children. In 68% of the samples identified at least one pathogen, in 12% of the samples were identified two or more pathogens. The analysis showed that the mixed infection prolongs hospitalization.
    Full-text · Conference Paper · Mar 2015
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    ABSTRACT: A series of new quaternary 1,4-diazabicyclo[2.2.2]octane derivatives was synthesized and evaluated for activity against several strains of both Gram positive and Gram negative bacteria and one strain of fungus under different inoculum size. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six species of microorganisms were tested. Results show a clear structure-activity relationship between alkyl chain length of substitutions of 1,4-diazabicyclo[2.2.2]octane tertiary amine sites and antimicrobial activity. In the case of compounds 4a-4k, MIC was found to decrease with the increase of the alkyl chain length from ethyl to dodecyl and then to increase at higher chain length (n > 14). The MIC values were found to be low for the compounds 4f and 4g with alkyl chains ranging from 10 to 12 carbons in length (1.6 μg/ml) and were comparable to the reference drug Ciprofloxacin. Also, time-kill assay was performed to examine the bactericidal kinetics. Results indicated that 4f and 4g had rapid killing effects against Staphylococcus aureus, and eliminated 100% of the initial inoculum of bacteria in 2.5 h at the concentration of 10 μg/ml. In addition, compound 4g eliminate more than 99.9% of the initial inoculum of Ps. aeruginosa after 2.5 h of interaction but the activity of compound 4f against this species seems to be weak. Thus, 4g had strong bactericidal activity and could rapidly kill Gram positive S. aureus, as well as Gram negative Ps. aeruginosa at low and high inoculum size. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Full-text · Article · Mar 2015 · European Journal of Medicinal Chemistry
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    ABSTRACT: This study used geological, geochemical, and microbiological data to examine the Uzon oils and conditions within the Uzon caldera. The trace-element compositions of crude oils and solutions from boreholes and hydrothermal springs were determined by ICP-MS. The majority of hydrothermal manifestations within the Uzon caldera are controlled by three trends of faults. The major fault zone, trending nearly E–W, is located between Kikhpinych and Taunshits volcanoes. It acts as a magma conduit and hosts numerous oval-shaped hydrothermal vents. The Oil site is situated on the periphery of the hottest area of highest hydrothermal activity within the Eastern thermal field. On the Eh–pH diagram, most solutions of the Uzon caldera define distinct fields and trends which correlate with the stability fields for sulfur and iron. The Oil site is characterized by very wide variations in temperature and Eh–pH parameters of pore solutions. The geochemical signatures of the solutions at this site are broadly similar to those from other areas of the Uzon caldera, but differ in their sulfide ion and sulfate ion concentrations. These differences can be explained by mixing of deep chloride-sodium hydrothermal solutions and solutions produced during surface oxidation of sulfide-containing material. With respect to the average continental crust, the Uzon oil is enriched in S, As, and Hg. The crude oil and solutions have broadly similar concentrations of B, S, Cl, As, Se, Br, Cd, I, Hg, and Pb and highly variable concentrations of Ti, V, Cr, Co, Ni, Cu, Cd, Nb, and Sn. The community structure of archaeal assemblages in springs and test pits at the Eastern thermal field was analyzed by 16S rRNA library and pyrosequencing methods. It was found that the proportion of archaea in the microbial communities of the Uzon caldera ranges from 2 to over 70% of the total sequences identified. Crenarchaeota were found in large proportions in all samples except one. The majority of the sequences in four samples were affiliated with Euryarchaeota, which comprise methanogenic archaea, extreme halophiles, and some extreme thermophiles. The results of geological, mineralogical-geochemical, microbiological and physicochemical studies of oil seeps in the Uzon caldera reveal distinctive geochemical characteristics of crude oil and the complexity of oil formation. © 2015, V.S. Sobolev IGM, Siberian Branch of the RAS. Published by Elsevier B.V. All rights reserved.
    Full-text · Article · Feb 2015 · Russian Geology and Geophysics
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    ABSTRACT: The complete genomes of two human bocavirus 4 (HBoV4) isolates recovered in 2011 in Novosibirsk, Russia have been determined. A set of primers was designed based on the determined and previously published HBoV sequences; this primer pair was able to detect all possible HBoV replicative intermediates. This primer set was used to assay all HBoV genotypes and detected only those structures that correspond to an episomal form of this viral genome. Also, for the first time, head-to-tail nucleotide sequences have been determined for HBoV4. Secondary structures of the terminal noncoding regions (NCRs) of episomal forms have been computed for all HBoV genotypes, as well as for the canine bocavirus. Conserved secondary structures in episomal NCRs, which are likely to play an important part in the replication of bocaviruses, were found. NCR heterogeneity in the genomes of individual HBoV isolates has been shown for the first time. Copyright © 2014 Elsevier B.V. All rights reserved.
    Full-text · Article · Jan 2015 · Virus Research

Publication Stats

215 Citations
132.82 Total Impact Points

Institutions

  • 2011-2016
    • Institute of Chemical Biology and Fundamental Medicine
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 2009-2015
    • Russian Academy of Sciences
      • Institute of Chemical Biology and Fundamental Medicine
      Moskva, Moscow, Russia
  • 2012
    • Novosibirsk State University
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 1999-2007
    • State Research Center of Virology and Biotechnology VECTOR
      Novo-Nikolaevsk, Novosibirsk, Russia