المؤلفون: Edyta Paradowska, Agnieszka Jabłońska, Mirosława Studzińska, Katarzyna Skowrońska, Patrycja Suski, Małgorzata Wiśniewska-Ligier, Teresa Woźniakowska-Gęsicka, Dorota Nowakowska, Zuzanna Gaj, Jan Wilczyński, Zbigniew J Leśnikowski

المصدر: PLoS ONE, Vol 11, Iss 4, p e0154100 (2016)

مصطلحات موضوعية: Medicine, Science

الوصف: Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni's correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4841553?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/966bdafe1ce0422eb4121fd1096cec3eTest

المؤلفون: Edyta Paradowska, Jarosław Kalinka, Maciej Cedzynski, Patrycja Suski, Agnieszka Jabłońska, Zbigniew J. Leśnikowski, Anna S. Świerzko, Mirosława Studzińska

المصدر: Molecular Immunology. 126:143-152

مصطلحات موضوعية: 0301 basic medicine, Human cytomegalovirus, Chemokine, Interferon-Induced Helicase, IFIH1, Placenta, Pregnancy Trimester, Third, viruses, medicine.medical_treatment, Immunology, Cytomegalovirus, Cell Line, Proinflammatory cytokine, Tissue Culture Techniques, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Pregnancy, medicine, Animals, Humans, Pregnancy Complications, Infectious, Receptors, Immunologic, Receptor, Molecular Biology, biology, Interferon-beta, Vesiculovirus, biology.organism_classification, medicine.disease, Virology, Infectious Disease Transmission, Vertical, 030104 developmental biology, Cytokine, Vesicular stomatitis virus, biology.protein, DEAD Box Protein 58, Female, RNA Helicases, Ex vivo, 030215 immunology

الوصف: A viral infection is detected through germline-encoded pattern-recognition receptors (PRRs) leading to the production of interferons (IFNs) and proinflammatory cytokines. The objective of this study was to investigate the expression of retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) in response to viral infection and the selected cytokine responses in the human term placenta. Placental villi and decidual explants were infected with human cytomegalovirus (CMV) or vesicular stomatitis virus (VSV) and cultured ex vivo to study viral infection. To evaluate DDX58 (RIG-I), IFIH1 (MDA5), and DHX58 (LGP2) expression, quantitative real-time PCR (qRT-PCR) was used. The expression of RLRs was detected by Western blotting. Cytokine and chemokine production, as well as RLR protein levels, were quantified using ELISA. The increased expression of both RIG-I and MDA5 and the enhanced secretion of IFN-s were observed in response to VSV infection compared to mock-infected tissues. CMV infection resulted in higher transcript levels of DDX58 and IFIH1, while no changes in the cytokine production were observed. Our results indicate that RIG-I and MDA5 are specifically expressed in chorionic villi and deciduae in response to VSV infection. These findings suggest that RLRs may play a key role in pathogen recognition and the immune response against intrauterine viral transmission.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b6fa95a0bc0e51dbf7edaa5ab2130deTest
https://doi.org/10.1016/j.molimm.2020.08.001Test

المؤلفون: Agnieszka, Jablonska, Patrycja, Suski, Miroslawa, Studzinska, Jaroslaw, Kalinka, Edyta, Paradowska

المصدر: Frontiers in Immunology ; volume 4 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.3389/conf.fimmu.2013.02.00293Test

المؤلفون: Patrycja, Suski, Jaroslaw, Kalinka, Miroslawa, Studzinska, Agnieszka, Jablonska, Zbigniew, Lesnikowski, Edyta, Paradowska

المصدر: Frontiers in Immunology ; volume 4 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الإتاحة: https://doi.org/10.3389/conf.fimmu.2013.02.00142Test

المؤلفون: Mirosława Studzińska, Jarosław Kalinka, Agnieszka Jabłońska, Patrycja Suski, Edyta Paradowska

المصدر: Clinical and Experimental Immunology. 193:255-263

مصطلحات موضوعية: Adult, 0301 basic medicine, Biopsy, Placenta, Pregnancy Trimester, Third, medicine.medical_treatment, Immunology, Herpesvirus 1, Human, Biology, Andrology, 03 medical and health sciences, Organ Culture Techniques, 0302 clinical medicine, Immune system, Pregnancy, Interferon, medicine, Humans, Immunology and Allergy, Pregnancy Complications, Infectious, Receptors, Immunologic, Cells, Cultured, Cesarean Section, Decidua, Nuclear Proteins, Trophoblast, Herpes Simplex, Original Articles, Phosphoproteins, Immunity, Innate, Up-Regulation, 030104 developmental biology, medicine.anatomical_structure, Cytokine, embryonic structures, TLR3, DEAD Box Protein 58, Chorionic villi, Female, 030215 immunology, medicine.drug

الوصف: Summary The innate immune response in the placenta depends on the ability of maternal immune cells and fetal trophoblast cells to detect and eliminate invading pathogens through germline-encoded pattern recognition receptors (PRRs). In the present study, we analysed the transcripts and protein expression of interferon (IFN)-inducible protein (IFI)16, melanoma differentiation-associated protein 5 (MDA5), RIG-I-like receptor (RIG-I) and Toll-like receptor (TLR)-3 in third-trimester human placentas and investigated cytokine profiles generated during herpes simplex type 1 (HSV-1) infection. Decidual and chorionic villous biopsies (38–42 weeks of gestation) were obtained from healthy women immediately after a caesarean section. The expression of the DDX58 (RIG-I), IFIH1 (MDA5), IFI16 and TLR3 transcripts was measured using quantitative real-time polymerase chain reaction (qRT–PCR). Extracellular cytokine and PRRs levels were then quantified by enzyme-linked immunosorbent assays (ELISAs). All examined PRRs genes, including DDX58, IFIH1, IFI16 and TLR3, were expressed constitutively at the mRNA and protein levels in the placental biopsies. The concentration of the IFI16 protein was increased in HSV-1-infected decidual and chorionic villous explants compared to those of mock-infected tissues (P = 0·029). Higher protein expression levels of RIG-I in both the maternal and fetal parts of the placenta were found (P = 0·009 and P = 0·004, respectively). In addition, increased production of IFN-β by HSV-1-infected tissues was noticed (P = 0·004 for decidua, P = 0·032 for chorionic villi). No significant differences in the IFN-α, interleukin (IL)-6 and IL-8 levels were found. These results showed that HSV-1 infection can enhance the expression of IFI16 and RIG-I proteins in the human term placenta.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::107270c9609e0aaf0a94cc3b78a3f685Test
https://doi.org/10.1111/cei.13143Test

المؤلفون: Zbigniew J. Leśnikowski, Patrycja Suski, Agnieszka Jabłońska, Edyta Paradowska, Mirosława Studzińska, Magdalena Białek-Pietras, Agnieszka B. Olejniczak

المصدر: Journal of Organometallic Chemistry. 798:99-105

مصطلحات موضوعية: Pyrimidine, Chemistry, Stereochemistry, Organic Chemistry, RNA, Sonogashira coupling, Biochemistry, In vitro, Inorganic Chemistry, chemistry.chemical_compound, Materials Chemistry, Carborane, Physical and Theoretical Chemistry, Cytotoxicity, Nucleoside, DNA

الوصف: A series of novel conjugates of para-carborane with 5-ethynyl-uridine or 2′-deoxyuridine were synthesized. The conjugates were prepared by Sonogashira coupling of para-carborane terminal alkynes and 5-iodo-nucleoside. The designed compounds demonstrated low to moderate cytotoxicity in several cell lines. The antiviral activities of the agents were measured against a panel of DNA and RNA viruses. The most potent compound reported is 5-[(1,12-dicarba-closo-dodecaboran-2-yl)ethyn-1-yl]-2′-deoxyuridine (8), with an IC50 value of 5.5 μM and a selectivity index higher than 180. This compound is unusual in that it exhibits antiviral activity against HCMV and is not active against HSV-1, HPIV-3 or EMCV.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0a5698e53e634533cec22bec1e3ef0d0Test
https://doi.org/10.1016/j.jorganchem.2015.07.002Test

المؤلفون: Barbara Zawilińska, Dorota Nowakowska, Edyta Paradowska, Zuzanna Gaj, Beata Kasztelewicz, Małgorzata Wiśniewska-Ligier, Patrycja Suski, Mirosława Studzińska

المصدر: Journal of Medical Virology. 87:1737-1748

مصطلحات موضوعية: Human cytomegalovirus, Congenital cytomegalovirus infection, Biology, medicine.disease, Asymptomatic, Virology, Infectious Diseases, Immune system, Immunology, Genotype, medicine, Gene polymorphism, medicine.symptom, Viral load, Genotyping

الوصف: Cytomegalovirus (CMV) is the most common cause of congenital infection. This pathogen exhibits extensive genetic variability in the genes that encode structural envelope glycoproteins, regulatory proteins, and proteins that contribute to immune evasion. However, the role of specific viral strains in the outcome of congenital CMV infection is unclear. Variation in the UL55 gene encoding glycoprotein B (gB), the UL144 gene encoding TNF α-like receptor, and the US28 gene encoding β-chemokine receptor was determined in 60 newborn infants with congenital CMV infection and 90 infants with postnatal or undefined CMV infection. CMV polymorphisms were studied in relation to disease outcome and viral load. Genotyping was performed by a sequencing analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. The results demonstrated that (1) the UL55 and US28 genotype distributions were similar among the group of congenital and postnatal CMV infection; (2) the UL144 B1 genotype was more prevalent in congenital than in postnatal infection and was detected in 70% of newborns with asymptomatic congenital infection; and (3) none of the examined genotype was significantly linked with symptomatic CMV infection. No relationship was observed between genotype and viral load. The results revealed that UL55, UL144, and US28 polymorphisms are not associated with the outcome of CMV infection in infants, but the presence of UL144 B1 genotype might be virological marker of asymptomatic infection at birth.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::f3effd2f10a0b83e3f40bfa7f2c6d777Test
https://doi.org/10.1002/jmv.24222Test

المؤلفون: M. Rycel, Barbara Zawilińska, Patrycja Suski, Jacek R. Wilczyński, Zuzanna Gaj, Zbigniew J. Leśnikowski, Dorota Nowakowska, Edyta Paradowska, Wioletta Wujcicka

المصدر: European Journal of Clinical Microbiology & Infectious Diseases

مصطلحات موضوعية: Microbiology (medical), Human cytomegalovirus, medicine.medical_specialty, Genotype, viruses, Congenital cytomegalovirus infection, Cytomegalovirus, Antibodies, Viral, Real-Time Polymerase Chain Reaction, Asymptomatic, Article, law.invention, Fetus, Medical microbiology, Viral Envelope Proteins, Pregnancy, law, Humans, Medicine, Pregnancy Complications, Infectious, Genotyping, Polymerase chain reaction, Immunoassay, Molecular Epidemiology, Coinfection, business.industry, Infant, Newborn, virus diseases, General Medicine, medicine.disease, Virology, Infectious Diseases, Cytomegalovirus Infections, Immunology, Female, Poland, medicine.symptom, business

الوصف: The purpose of this investigation was to describe a distribution of cytomegalovirus (CMV) single and multiple genotypes among infected pregnant women, their fetuses, and newborns coming from Central Poland, as well as congenital cytomegaly outcome. The study involved 278 CMV-seropositive pregnant women, of whom 192 were tested for viral DNAemia. Human cytomegalovirus (HCMV) genotyping was performed for 18 of 34 pregnant women carrying the viral DNA and for 12 of their 15 offspring with confirmed HCMV infections. Anti-HCMV antibodies levels were assessed by chemiluminescence immunoassay (CLIA) and enzyme-linked fluorescence assay (ELFA) tests. Viral DNA loads and genotypes were determined by real-time polymerase chain reaction (PCR) assays for the UL55 gene. In the pregnant women, we identified HCMV gB1, gB2, gB3, and gB4 genotypes. Single gB2, gB3, or gB4 genotypes were observed in 14 (77.8 %) women, while multiple gB1–gB2 or gB2–gB3 genotypes were observed in four (22.2 %). Maternal HCMV genotypes determined the genotypes identified in their fetuses and newborns (p ≤ 0.050). Half of them were infected with single HCMV gB1, gB2, or gB3 genotypes and the other half with multiple gB1–gB2 or gB2–gB3 genotypes. Single and multiple genotypes were observed in both asymptomatic and symptomatic congenital cytomegaly, although no gB3 genotype was identified among asymptomatic cases. In Central Poland, infections with single and multiple HCMV strains occur in pregnant women, as well as in their fetuses and neonates, with both asymptomatic and symptomatic infections. HCMV infections identified in mothers seem to be associated with the viral genotypes in their children.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::810ba703eae5ec3ea891b4bba1fca6e7Test
https://doi.org/10.1007/s10096-014-2266-9Test

المؤلفون: Agnieszka Płóciennikowska, Mirosława Studzińska, Małgorzata Wiśniewska-Ligier, Zbigniew J. Leśnikowski, Teresa Woźniakowska-Gęsicka, Katarzyna Dzierżanowska-Fangrat, Agnieszka Jabłońska, Edyta Paradowska, Patrycja Suski, Beata Kasztelewicz

المصدر: Virology. :207-217

مصطلحات موضوعية: Adult, Male, Human cytomegalovirus, Genotype, viruses, Congenital cytomegalovirus infection, Cytomegalovirus, Biology, Viral Proteins, Viral Envelope Proteins, Congenital infection, Virology, Postnatal infection, medicine, Humans, Alpha Chemokine, Gene, Glycoproteins, Infant, Newborn, Genetic Variation, Infant, virus diseases, Viral Load, medicine.disease, Virus genotype, Congenital infections, Cytomegalovirus Infections, Immunology, Female, Chemokines, CXC, Viral load, α-chemokine

الوصف: Human cytomegalovirus (HCMV) is the leading cause of congenital infections. The aim of our study was to determine the prevalence of genotypes based on the highly polymorphic UL146 and UL147 HCMV genes and the relationship between the genotype and symptoms or viral load.We analyzed samples from 121 infants with symptomatic HCMV infection, including 32 congenitally infected newborns. The G7 and G5 genotypes were predominant in postnatal infection, whereas the G1 genotype was prevalent in congenital infection. Central nervous system (CNS) damage and hepatomegaly were detected more frequently among children infected with the G1 genotype than in those infected by other genotypes. An association between the viral genotype and viruria level was found. There was a strong correlation between HCMV genotypes determined through the UL146 and UL147 sequences (ĸ=0.794).In conclusion, we found that certain vCXCL genotypes are associated with clinical sequelae following HCMV infection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26c1fd8d5811755db43e537c0fca0fb4Test

المؤلفون: Edyta Paradowska, Patrycja Suski, Małgorzata Wiśniewska-Ligier, Teresa Woźniakowska-Gęsicka, Dorota Nowakowska, Jan Wilczyński, Zbigniew J. Leśnikowski, Agnieszka Jabłońska, Mirosława Studzińska

المصدر: International Journal of Infectious Diseases. 25:11-15

مصطلحات موضوعية: Adult, Male, Human cytomegalovirus, Microbiology (medical), Genotype, Cytomegalovirus, Single-nucleotide polymorphism, Biology, medicine.disease_cause, Polymorphism, Single Nucleotide, Loss of heterozygosity, Young Adult, Gene Frequency, Risk Factors, Odds Ratio, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Codon, Genotyping, Alleles, Aged, Infant, Newborn, Infant, virus diseases, General Medicine, Middle Aged, Viral Load, medicine.disease, Virology, Toll-Like Receptor 2, Toll-like receptors, Toll-Like Receptor 4, Infectious Diseases, Amino Acid Substitution, Cytomegalovirus Infections, Immunology, Female, Viral load

الوصف: SummaryObjectivesThe association among specific single-nucleotide polymorphisms (SNPs) in TLR2 (Arg677Trp, Arg753Gln) and TLR4 (Asp299Gln) and human cytomegalovirus (CMV) infection was studied in infants and adults.MethodsThe TLR2 and TLR4 polymorphisms were genotyped in 151 patients with CMV infections and in 78 unrelated healthy individuals. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis of PCR-amplified fragments. The viral load was measured by quantitative real-time PCR.ResultsAlmost all of the patients with CMV infections were wild-type homozygotes without TLR2 and TLR4 polymorphisms. No significant differences in TLR2 and TLR4 polymorphisms were observed between infants with or without CMV infection. Compared with adults with CMV infections, heterozygosity for the TLR2 Arg677Trp and TLR4 Asp299Gly SNPs was detected more frequently in healthy individuals (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf29758ff5277a239275bf053fcd72f0Test