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Browsing by Author "Jovanovic, Tanja (26642921700)"

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    Analysis of the variability of Epstein-Barr virus genes in infectious mononucleosis: Investigation of the potential correlation with biochemical parameters of hepatic involvement
    (2016)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Cirkovic, Andja (56120460600)
    ;
    Karalic, Danijela (57403944300)
    ;
    Cupic, Maja (15730255400)
    ;
    Banko, Bojan (35809871900)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Jovanovic, Tanja (26642921700)
    Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.
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    Analysis of the variability of Epstein-Barr virus genes in infectious mononucleosis: Investigation of the potential correlation with biochemical parameters of hepatic involvement
    (2016)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Cirkovic, Andja (56120460600)
    ;
    Karalic, Danijela (57403944300)
    ;
    Cupic, Maja (15730255400)
    ;
    Banko, Bojan (35809871900)
    ;
    Milovanovic, Jovica (6603250148)
    ;
    Jovanovic, Tanja (26642921700)
    Background: Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters. Methods: The study included plasma samples from 128 IM patients. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. Results: The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes of LMP1 isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, deleted LMP1/P-thr and non-deleted LMP1/P-ala, as well as genotype 1/ 4.5 33-bp LMP1 repeats or genotype 2/ 4.5 33-bp LMP1 repeats showed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase). Conclusions: This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers. © by Ana Banko 2016.
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    Analysis of variability of urinary excreted JC virus strains in patients infected with HIV and healthy donors
    (2018)
    Karalic, Danijela (57403944300)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Banko, Ana (35774145100)
    ;
    Cupic, Maja (15730255400)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Jovanovic, Tanja (26642921700)
    In immunocompromised individuals, especially in patients with T cell immunodeficiency, reactivation of JCPyV can cause serious life-threatening diseases. Nowadays, HIV infection is one of the most important factor for reactivation of JCPyV and the development of of the progressive multifocal leukoencephalopathy (PML). Mutations in the outer loops of the VP1 region can lead to the selection of the viral variants with changed tropism and increased pathological potential. The aims of this study were to determine sequence variation and amino acid changes within VP1 loops and the structure of non-coding control region (NCCR) of urinary excreted JCPyV isolates among HIV-infected patients and healthy donors. Single urine samples from 114 HIV-infected patients and 120 healthy donors were collected. PCR was performed for amplification of VP1 and NCCR. Amplified fragments were directly sequenced and analyzed by using bioinformatics tools. Nucleotide substitutions were detected within DE and EF loops and in the β-sheets of both studied groups. In HIV-infected patients group, 70% of mutations were detected within receptor domains. Among healthy donors, one mutation was identified within β-sheets while the remaining were located within receptor domains. The most prevalent mutation was L157V in both groups. Analysis of NCCR revealed that all isolates had archetype structure with some minor changes. Since single point mutations at specific place within outer loop of VP1 region can cause formation of variants with changed receptor specificity, identification of these mutations in HIV-infected patients can help to single out those with higher risk for development of polyomavirus-associated diseases. © 2017, Journal of NeuroVirology, Inc.
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    Analysis of variability of urinary excreted JC virus strains in patients infected with HIV and healthy donors
    (2018)
    Karalic, Danijela (57403944300)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Banko, Ana (35774145100)
    ;
    Cupic, Maja (15730255400)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Jovanovic, Tanja (26642921700)
    In immunocompromised individuals, especially in patients with T cell immunodeficiency, reactivation of JCPyV can cause serious life-threatening diseases. Nowadays, HIV infection is one of the most important factor for reactivation of JCPyV and the development of of the progressive multifocal leukoencephalopathy (PML). Mutations in the outer loops of the VP1 region can lead to the selection of the viral variants with changed tropism and increased pathological potential. The aims of this study were to determine sequence variation and amino acid changes within VP1 loops and the structure of non-coding control region (NCCR) of urinary excreted JCPyV isolates among HIV-infected patients and healthy donors. Single urine samples from 114 HIV-infected patients and 120 healthy donors were collected. PCR was performed for amplification of VP1 and NCCR. Amplified fragments were directly sequenced and analyzed by using bioinformatics tools. Nucleotide substitutions were detected within DE and EF loops and in the β-sheets of both studied groups. In HIV-infected patients group, 70% of mutations were detected within receptor domains. Among healthy donors, one mutation was identified within β-sheets while the remaining were located within receptor domains. The most prevalent mutation was L157V in both groups. Analysis of NCCR revealed that all isolates had archetype structure with some minor changes. Since single point mutations at specific place within outer loop of VP1 region can cause formation of variants with changed receptor specificity, identification of these mutations in HIV-infected patients can help to single out those with higher risk for development of polyomavirus-associated diseases. © 2017, Journal of NeuroVirology, Inc.
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    Carboxy-terminal sequence variation of LMP1 gene in Epstein-Barr-virus-associated mononucleosis and tumors from Serbian patients
    (2012)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Cupic, Maja (15730255400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Boricic, Ivan (6603959716)
    ;
    Jovanovic, Tanja (26642921700)
    Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.
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    Carboxy-terminal sequence variation of LMP1 gene in Epstein-Barr-virus-associated mononucleosis and tumors from Serbian patients
    (2012)
    Banko, Ana (35774145100)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Cupic, Maja (15730255400)
    ;
    Stevanovic, Goran (15059280200)
    ;
    Boricic, Ivan (6603959716)
    ;
    Jovanovic, Tanja (26642921700)
    Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates. © 2012 Wiley Periodicals, Inc.
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    Developing COVID-19 vaccine recommendations during the pandemic: The experience of Serbia's Expert Committee on Immunization
    (2022)
    Markovic-Denic, Ljiljana (55944510900)
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    Popadic, Dusan (6602255798)
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    Jovanovic, Tanja (26642921700)
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    Bonaci-Nikolic, Branka (10839652200)
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    Samardzic, Janko (23987984500)
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    Tomic Spiric, Vesna (6603500319)
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    Rancic, Miljan (57992502100)
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    Sankar Datta, Siddhartha (57217159355)
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    Mosina, Liudmila (43161421300)
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    Jancic, Jasna (35423853400)
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    Vukomanovic, Goran (8252832300)
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    Jovanovic, Verica (56566176800)
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    Vukomanovic, Vladislav (55881072000)
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    Antic, Darko (23979576100)
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    Veljkovic, Marko (57188659157)
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    Saponjic, Vladan (57730308500)
    ;
    Jacques-Carroll, Lisa (24528511600)
    A National Immunization Technical Advisory Group (NITAG) is a multi-disciplinary body of national experts that provide evidence-based recommendations to policy-makers to assist them in making informed immunization policy and programme decisions. During the COVID-19 pandemic, NITAGs faced many challenges in making evidence-based recommendations for COVID-19 vaccines due to the rapidly evolving situation with new vaccine products available in a short time period and limited data on vaccine effectiveness. The authors reviewed the process used by Serbia's NITAG, which is called the Serbian Expert Committee on Immunization, to develop COVID-19 vaccine recommendations during the pandemic. The article examines the challenges and successes faced by the committee. Serbia's expert committee used the best available evidence to develop over forty recommendations on all aspects of COVID-19 vaccination. These expert committee recommendations facilitated the early procurement and successful roll-out of COVID-19 vaccines, guidance for vaccination of individuals at the highest risk, and high COVID-19 vaccination coverage in the country. The availability of five COVID-19 vaccines in Serbia was an advantage for the successful roll-out but posed challenges for the expert committee. Serbia's expert committee plans to use the experience and best practices developed during the pandemic to improve and expand its work moving forward. Copyright © 2022 Markovic-Denic, Popadic, Jovanovic, Bonaci-Nikolic, Samardzic, Tomic Spiric, Rancic, Sankar Datta, Mosina, Jancic, Vukomanovic, Jovanovic, Vukomanovic, Antic, Veljkovic, Saponjic and Jacques-Carroll.
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    Disseminated neonatal herpes caused by herpes simplex virus types 1 and 2
    (2007)
    Knezevic, Aleksandra (22034890600)
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    Martic, Jelena (19639196900)
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    Stanojevic, Maja (57828665700)
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    Jankovic, Sasa (57196854515)
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    Nedeljkovic, Jasminka (7003632043)
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    Nikolic, Ljubica (59847905000)
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    Pasic, Srdjan (55904557400)
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    Jankovic, Borisav (7005898688)
    ;
    Jovanovic, Tanja (26642921700)
    Disseminated neonatal herpes simplex virus (HSV) infection is characterized by progressive multiple organ failure and high mortality rates. It can result from infection with either HSV-1 or HSV-2. We report a case of disseminated neonatal herpes that was caused by HSV-1 and HSV-2.
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    Distribution of JC virus genotypes among serbian patients infected with HIV and in healthy donors
    (2014)
    Karalic, Danijela (57403944300)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Knezevic, Aleksandra (22034890600)
    ;
    Cupic, Maja (15730255400)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Jovanovic, Tanja (26642921700)
    Certain factors lead to increased reactivation of JC virus (JCV) and immunodeficiency seems to be the most important. JCV isolates can be classified into eight different genotypes and several subtypes based on nucleotide difference in the VP1 gene. JCV genotypes are strongly associated with particular ethnic groups and frequently used as genetic markers for human evolution and migration. The aim of this study was to determine the frequency of JCV urinary shedding and genotype distribution in Serbia among patients infected with HIV and healthy donors. Urine samples from 107 healthy donors and 93 patients infected with HIV were collected. PCR followed by sequence analysis was carried out using primers specific for VP1 and NCRR of the virus genome. Excretion rate of JCV-DNA in urine was higher in patients infected with HIV than in healthy donors (44.1% vs. 31.7%) although statistical significance was not found. Within the group infected with HIV, the degree of immunosuppression (measured by CD4+ cell count) did not influence JCV excretion rate. Sequence analysis of JCV NCRR from both patients infected with HIV and healthy donors showed a pattern identical to archetype structure. In healthy Serbian donors the predominant genotype was 1 (41.2%), followed by 4 (32.4%) and 2 (26.4%). On the other hand, genotype distribution pattern was different in patients infected with HIV: 2 (43.9%), 1 (31.7%), and 4 (24.4%). This study showed that European, Eurasian, and Indian types are circulating in Serbia and that distribution corresponds to the origin of the inhabitants of Serbia. J. Med. Virol. 86:411-418, 2014. © 2013 Wiley Periodicals, Inc.
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    Distribution of JC virus genotypes among serbian patients infected with HIV and in healthy donors
    (2014)
    Karalic, Danijela (57403944300)
    ;
    Lazarevic, Ivana (23485928400)
    ;
    Knezevic, Aleksandra (22034890600)
    ;
    Cupic, Maja (15730255400)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Jovanovic, Tanja (26642921700)
    Certain factors lead to increased reactivation of JC virus (JCV) and immunodeficiency seems to be the most important. JCV isolates can be classified into eight different genotypes and several subtypes based on nucleotide difference in the VP1 gene. JCV genotypes are strongly associated with particular ethnic groups and frequently used as genetic markers for human evolution and migration. The aim of this study was to determine the frequency of JCV urinary shedding and genotype distribution in Serbia among patients infected with HIV and healthy donors. Urine samples from 107 healthy donors and 93 patients infected with HIV were collected. PCR followed by sequence analysis was carried out using primers specific for VP1 and NCRR of the virus genome. Excretion rate of JCV-DNA in urine was higher in patients infected with HIV than in healthy donors (44.1% vs. 31.7%) although statistical significance was not found. Within the group infected with HIV, the degree of immunosuppression (measured by CD4+ cell count) did not influence JCV excretion rate. Sequence analysis of JCV NCRR from both patients infected with HIV and healthy donors showed a pattern identical to archetype structure. In healthy Serbian donors the predominant genotype was 1 (41.2%), followed by 4 (32.4%) and 2 (26.4%). On the other hand, genotype distribution pattern was different in patients infected with HIV: 2 (43.9%), 1 (31.7%), and 4 (24.4%). This study showed that European, Eurasian, and Indian types are circulating in Serbia and that distribution corresponds to the origin of the inhabitants of Serbia. J. Med. Virol. 86:411-418, 2014. © 2013 Wiley Periodicals, Inc.
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    HIV-1 subtypes in Yugoslavia
    (2002)
    Stanojevic, Maja (57828665700)
    ;
    Papa, Anna (7103044603)
    ;
    Papadimitriou, Evagelia (36017181000)
    ;
    Zerjav, Sonja (6603691730)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Salemovic, Dubravka (7801387340)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Antoniadis, Antonis (7006976281)
    To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.
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    HIV-1 subtypes in Yugoslavia
    (2002)
    Stanojevic, Maja (57828665700)
    ;
    Papa, Anna (7103044603)
    ;
    Papadimitriou, Evagelia (36017181000)
    ;
    Zerjav, Sonja (6603691730)
    ;
    Jevtovic, Djordje (55410443900)
    ;
    Salemovic, Dubravka (7801387340)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Antoniadis, Antonis (7006976281)
    To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.
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    Immunoblot analysis of natural and vaccine-induced IgG responses to rubella virus proteins expressed in insect cells
    (1999)
    Nedeljkovic, Jasminka (7003632043)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Mladjenovic, Srecko (6504609569)
    ;
    Hedman, Klaus (7006799529)
    ;
    Peitsaro, Nina (6603146307)
    ;
    Oker-Blom, Christian (7004056386)
    Background: The three structural proteins of rubella virus (RV), the capsid protein C and the envelope glycoproteins E1 and E2, were produced individually in soluble form in Sf9 insect cells using the baculovirus system. All proteins were equipped with a polyhistidine tag at their C-terminal ends to enable gentle purification by metal ion affinity chromatography. In addition, the E1 and E2 proteins were engineered to display the FLAG epitope tag at their N-terminal ends. Study design: The diagnostic potential of the recombinant purified proteins was evaluated by immunoblot and enzyme immuno assays (EIA) using a total of 57 well-characterised serum samples obtained at various time points after natural RV infection, congenital rubella syndrome (CRS), MMR vaccination or from controls with past RV immunity. In addition, acute and convalescent phase serum pools from a total of 20 patients were evaluated. Authentic RV proteins were used as a reference. Results: The recombinant E1 and C proteins were predominant in eliciting the immune responce in both postnatal and vaccinal RV infections, being much weaker in the vaccinal ones. The IgG responce to the recombinant C protein was very strong after the first month post infection and decreased with time. The immune responce against the recombinant E2 protein, however, was generally poor, but notably stronger after congenital infection. Together, the results showed that the individual recombinant protein antigens could be suitable for diagnosis of RV infection and for study of the immune response to rubella vaccination. Copyright (C) 1999 Elsevier Science B.V.
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    Immunoblot analysis of natural and vaccine-induced IgG responses to rubella virus proteins expressed in insect cells
    (1999)
    Nedeljkovic, Jasminka (7003632043)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Mladjenovic, Srecko (6504609569)
    ;
    Hedman, Klaus (7006799529)
    ;
    Peitsaro, Nina (6603146307)
    ;
    Oker-Blom, Christian (7004056386)
    Background: The three structural proteins of rubella virus (RV), the capsid protein C and the envelope glycoproteins E1 and E2, were produced individually in soluble form in Sf9 insect cells using the baculovirus system. All proteins were equipped with a polyhistidine tag at their C-terminal ends to enable gentle purification by metal ion affinity chromatography. In addition, the E1 and E2 proteins were engineered to display the FLAG epitope tag at their N-terminal ends. Study design: The diagnostic potential of the recombinant purified proteins was evaluated by immunoblot and enzyme immuno assays (EIA) using a total of 57 well-characterised serum samples obtained at various time points after natural RV infection, congenital rubella syndrome (CRS), MMR vaccination or from controls with past RV immunity. In addition, acute and convalescent phase serum pools from a total of 20 patients were evaluated. Authentic RV proteins were used as a reference. Results: The recombinant E1 and C proteins were predominant in eliciting the immune responce in both postnatal and vaccinal RV infections, being much weaker in the vaccinal ones. The IgG responce to the recombinant C protein was very strong after the first month post infection and decreased with time. The immune responce against the recombinant E2 protein, however, was generally poor, but notably stronger after congenital infection. Together, the results showed that the individual recombinant protein antigens could be suitable for diagnosis of RV infection and for study of the immune response to rubella vaccination. Copyright (C) 1999 Elsevier Science B.V.
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    Maturation of IgG avidity to individual rubella virus structural proteins
    (2001)
    Nedeljkovic, Jasminka (7003632043)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Oker-Blom, Christian (7004056386)
    Background: the structural proteins of rubella virus, the capsid protein C and the envelope glycoproteins E1 and E2 were produced in lepidopteran insect cells using baculovirus expression vectors. The C-terminal ends of the corresponding proteins were fused to a polyhistidine tag for easy and gentle purification by metal ion affinity chromatography. Objectives: to investigate the maturation of natural and vaccinal IgG avidity against individual authentic and recombinant rubella virus (RV) structural proteins. Study design: the analysis was carried out using a modified immunoblotting technique where the purified baculovirus-expressed proteins were compared with authentic rubella virus proteins. Altogether, 47 well-characterised serum samples from both naturally infected patients and vaccines were studied. Results: after natural RV infection, IgG antibodies specific for the E1 protein were predominant not only in terms of levels, but also in terms of rate and magnitude of avidity maturation. The avidity development of the IgG antibodies was much slower in vaccines than in patients after a natural RV infection. Conclusions: together, our results indicate that IgG avidity determination in conjunction with immunoblot analysis is useful in the diagnosis of a RV infection. The recombinant proteins showed similar reactivity patterns in the immunoblot analyses as compared with the authentic viral structural proteins, suggesting suitability for serodiagnostics. Copyright © 2001 Elsevier Science B.V.
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    Maturation of IgG avidity to individual rubella virus structural proteins
    (2001)
    Nedeljkovic, Jasminka (7003632043)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Oker-Blom, Christian (7004056386)
    Background: the structural proteins of rubella virus, the capsid protein C and the envelope glycoproteins E1 and E2 were produced in lepidopteran insect cells using baculovirus expression vectors. The C-terminal ends of the corresponding proteins were fused to a polyhistidine tag for easy and gentle purification by metal ion affinity chromatography. Objectives: to investigate the maturation of natural and vaccinal IgG avidity against individual authentic and recombinant rubella virus (RV) structural proteins. Study design: the analysis was carried out using a modified immunoblotting technique where the purified baculovirus-expressed proteins were compared with authentic rubella virus proteins. Altogether, 47 well-characterised serum samples from both naturally infected patients and vaccines were studied. Results: after natural RV infection, IgG antibodies specific for the E1 protein were predominant not only in terms of levels, but also in terms of rate and magnitude of avidity maturation. The avidity development of the IgG antibodies was much slower in vaccines than in patients after a natural RV infection. Conclusions: together, our results indicate that IgG avidity determination in conjunction with immunoblot analysis is useful in the diagnosis of a RV infection. The recombinant proteins showed similar reactivity patterns in the immunoblot analyses as compared with the authentic viral structural proteins, suggesting suitability for serodiagnostics. Copyright © 2001 Elsevier Science B.V.
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    Nijmegen breakage syndrome and chronic polyarthritis
    (2013)
    Pasic, Srdjan (55904557400)
    ;
    Cupic, Maja (15730255400)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Djukic, Slobodanka (6603568490)
    ;
    Kavaric, Maja (55853544500)
    ;
    Lazarevic, Ivana (23485928400)
    We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur. In our patient microbiologic cultures of synovial fluid including Mycoplasma spp. were negative. At first, because of suspected mycoplasmal arthritis we used macrolides and doxycycline combined with hydroxychloroquine but without therapeutic response. However, the use of rituximab led to remission of her polyarthritis lasting for 9 months. Autoimmune features were rarely reported in NBS. An occurrence of JIA-like, chronic polyarthritis in NBS, a DNA repair disorder characterized by decreased tolerance of immunosuppressive drugs such as methotrexate and a high natural risk for lymphomas, makes therapeutic approach even more complex. © 2013 Pasic et al.; licensee BioMed Central Ltd.
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    Prevalence of hepatitis B virus MHR mutations and their correlation with genotypes and antiviral therapy in chronically infected patients in Serbia
    (2010)
    Lazarevic, Ivana (23485928400)
    ;
    Cupic, Maja (15730255400)
    ;
    Delic, Dragan (55886413300)
    ;
    Svirtlih, Neda Stojkovic (6603664119)
    ;
    Simonovic, Jasmina (6507086058)
    ;
    Jovanovic, Tanja (26642921700)
    Understanding the prevalence and diversity of HBsAg variants in a population is fundamental to assay design and planning vaccination programs. It has been shown that mutations within the S gene, caused by selection or natural variation, can lead to false-negative results in assays for HBsAg, or have clinical implications, such as evading anti-HBV immunoglobulin therapy or vaccine-induced immunity. The region of HBsAg where most of these mutations occur is known as the major hydrophilic region (MHR). The aim of this study was to determine the prevalence and mutational patterns of MHR mutations in patients with chronic hepatitis B, and their correlation with patient characteristics, viral factors and antiviral therapy. The study comprised 164 plasma samples from patients with chronic hepatitis B, of which, 34.8% were on long-term lamivudine monotherapy. Direct sequencing of part of the S/pol gene was used for identification of HBsAg mutations, HBV genotypes, subgenotypes and HBsAg subtypes. The overall frequency of MHR mutations was 22.6%, but it varied significantly between untreated and treated patients (16.8% vs. 33.3%). The most frequent substitution was at position 120 (9.1%) whereas the most common vaccine-escape position, 145, was affected in 1.8% of isolates. The presence of MHR mutations was correlated with genotype D, subgenotype D3, and ayw2/ayw3 HBsAg subtypes and to older age (>40 years). It is concluded that natural viral variability present in a geographical region, duration of infection, and antiviral therapy are among the major factors associated with the occurrence of MHR mutations. © 2010 Wiley-Liss, Inc.
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    Prevalence of hepatitis B virus MHR mutations and their correlation with genotypes and antiviral therapy in chronically infected patients in Serbia
    (2010)
    Lazarevic, Ivana (23485928400)
    ;
    Cupic, Maja (15730255400)
    ;
    Delic, Dragan (55886413300)
    ;
    Svirtlih, Neda Stojkovic (6603664119)
    ;
    Simonovic, Jasmina (6507086058)
    ;
    Jovanovic, Tanja (26642921700)
    Understanding the prevalence and diversity of HBsAg variants in a population is fundamental to assay design and planning vaccination programs. It has been shown that mutations within the S gene, caused by selection or natural variation, can lead to false-negative results in assays for HBsAg, or have clinical implications, such as evading anti-HBV immunoglobulin therapy or vaccine-induced immunity. The region of HBsAg where most of these mutations occur is known as the major hydrophilic region (MHR). The aim of this study was to determine the prevalence and mutational patterns of MHR mutations in patients with chronic hepatitis B, and their correlation with patient characteristics, viral factors and antiviral therapy. The study comprised 164 plasma samples from patients with chronic hepatitis B, of which, 34.8% were on long-term lamivudine monotherapy. Direct sequencing of part of the S/pol gene was used for identification of HBsAg mutations, HBV genotypes, subgenotypes and HBsAg subtypes. The overall frequency of MHR mutations was 22.6%, but it varied significantly between untreated and treated patients (16.8% vs. 33.3%). The most frequent substitution was at position 120 (9.1%) whereas the most common vaccine-escape position, 145, was affected in 1.8% of isolates. The presence of MHR mutations was correlated with genotype D, subgenotype D3, and ayw2/ayw3 HBsAg subtypes and to older age (>40 years). It is concluded that natural viral variability present in a geographical region, duration of infection, and antiviral therapy are among the major factors associated with the occurrence of MHR mutations. © 2010 Wiley-Liss, Inc.
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    Prevalence of oral herpes simplex virus reactivation in cancer patients: A comparison of different techniques of viral detection
    (2009)
    Djuric, Milanko (8838562400)
    ;
    Jankovic, Ljiljana (7006253631)
    ;
    Jovanovic, Tanja (26642921700)
    ;
    Pavlica, Dusan (15849034500)
    ;
    Brkic, Snezana (58119094400)
    ;
    Knezevic, Aleksandra (22034890600)
    ;
    Markovic, Dubravka (7004487104)
    ;
    Milasin, Jelena (6603015594)
    Background: Oral reactivation of latent Herpes simplex virus (HSV) infection may easily occur in cancer patients. Virus reactivation can cause oral mucosa damage, worsen already existing lesions caused by stomatotoxic effect of cancer therapy and, whether symptomatic or asymptomatic, ample spreading and promote viral transmission. Methods: Polymerase chain reaction (PCR), cell-culture and direct immunofluorescence have been used to determine the frequency of oral HSV reactivation in 60 patients undergoing chemotherapy for different malignancies. Results: By means of PCR, the presence of viral DNA was detected in 71.7% of patients prior to chemotherapy and in 85.0% after chemotherapy. 33.3% of patients before and 40.0% after chemotherapy were viral-culture positive, while 3.3% of patients before and 11.7% after chemotherapy were positive as shown by direct immunofluorescence. No significant difference in HSV-1 reactivation was found before and after chemotherapy. In addition, no significant difference was found when comparing HSV-1 reactivation in patients with and without mucositis. HSV-2 was not detected in any of the patients. Conclusions: Reactivation of latent HSV is exceptionally frequent in cancer patients. The results of this study suggest that virus reactivation occurs independently of cancer chemotherapy. The potential role of HSV reactivation in oral mucosa damage remains unclear. © 2008 Blackwell Munksgaard.
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