Phylogenetic anaysis and molecular evolution of highly variable viruses: coinfections, host-pathogene interactions

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Phylogenetic anaysis and molecular evolution of highly variable viruses: coinfections, host-pathogene interactions (en)
Филогенетски приступ анализи молекуларне еволуције високо варијабилних вируса - коинфекције, интеракција вируса и домаћина (sr)
Filogenetski pristup analizi molekularne evolucije visoko varijabilnih virusa - koinfekcije, interakcija virusa i domaćina (sr_RS)
Authors

Publications

Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011.

Stanojević, Maja; Ćirković, Valentina; Siljić, Marina; Gligić, Ana; Stamenković, Gorana

(2019)

TY  - JOUR
AU  - Stanojević, Maja
AU  - Ćirković, Valentina
AU  - Siljić, Marina
AU  - Gligić, Ana
AU  - Stamenković, Gorana
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S187603411930108X?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3316
AB  - BACKGROUND Hantaviruses are etiological agents of emerging zoonotic diseases worldwide, including hemorrhagic fever with renal syndrome (HFRS). A number of hantavirus species is known to be present in Europe. In Serbia, existing data on hantavirus presence and prevalence rely in serological findings. In this study, molecular analysis was performed in order to characterize HFRS causing hantaviruses in Serbia. METHODS Sixty four serum samples of HFRS cases, previously found seropositive to anti-hantaviral antibodies, were included in the study. Partial hantaviral L and S segments were PCR amplified producing 390nt and 598nt amplicons, respectively, in parallel with human beta-actin mRNA as external reverse transcription positive control. Hantavirus specific PCR products were DNA sequenced in both direction and the obtained sequences phylogenetically confirmed and analyzed. RESULTS PCR detection of hantavirus L and S genome segments was positive in 18/64 and 11/64 tested samples, respectively. Positive PCR results involved samples obtained from different locations, mostly from central and southern parts of Serbia. All the obtained sequences were identified as Dobrava-Belgrade virus (DOBV). In the phylogenetic analysis sequences from Serbia tended to cluster in distinctive, geographically related clusters. CONCLUSIONS Our findings indicate DOBV as the main HFRS causing hantavirus in Serbia, the site of its initial isolation.
T2  - Journal of Infection and Public Health
T1  - Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011.
DO  - 10.1016/j.jiph.2019.02.021
ER  - 
@article{
author = "Stanojević, Maja and Ćirković, Valentina and Siljić, Marina and Gligić, Ana and Stamenković, Gorana",
year = "2019",
abstract = "BACKGROUND Hantaviruses are etiological agents of emerging zoonotic diseases worldwide, including hemorrhagic fever with renal syndrome (HFRS). A number of hantavirus species is known to be present in Europe. In Serbia, existing data on hantavirus presence and prevalence rely in serological findings. In this study, molecular analysis was performed in order to characterize HFRS causing hantaviruses in Serbia. METHODS Sixty four serum samples of HFRS cases, previously found seropositive to anti-hantaviral antibodies, were included in the study. Partial hantaviral L and S segments were PCR amplified producing 390nt and 598nt amplicons, respectively, in parallel with human beta-actin mRNA as external reverse transcription positive control. Hantavirus specific PCR products were DNA sequenced in both direction and the obtained sequences phylogenetically confirmed and analyzed. RESULTS PCR detection of hantavirus L and S genome segments was positive in 18/64 and 11/64 tested samples, respectively. Positive PCR results involved samples obtained from different locations, mostly from central and southern parts of Serbia. All the obtained sequences were identified as Dobrava-Belgrade virus (DOBV). In the phylogenetic analysis sequences from Serbia tended to cluster in distinctive, geographically related clusters. CONCLUSIONS Our findings indicate DOBV as the main HFRS causing hantavirus in Serbia, the site of its initial isolation.",
journal = "Journal of Infection and Public Health",
title = "Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011.",
doi = "10.1016/j.jiph.2019.02.021"
}
Stanojević, M., Ćirković, V., Siljić, M., Gligić, A.,& Stamenković, G.. (2019). Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011.. in Journal of Infection and Public Health.
https://doi.org/10.1016/j.jiph.2019.02.021
Stanojević M, Ćirković V, Siljić M, Gligić A, Stamenković G. Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011.. in Journal of Infection and Public Health. 2019;.
doi:10.1016/j.jiph.2019.02.021 .
Stanojević, Maja, Ćirković, Valentina, Siljić, Marina, Gligić, Ana, Stamenković, Gorana, "Molecular characterization of Dobrava-Belgrade hantavirus in Serbia, 2007-2011." in Journal of Infection and Public Health (2019),
https://doi.org/10.1016/j.jiph.2019.02.021 . .
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Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.

Li, Kun; Stanojević, Maja; Stamenković, Gorana; Ilić, Bojan; Paunović, Milan; Lu, Miao; Pešić, Branislav; Đurić Maslovara, Ivana; Siljic, Marina; Cirkovic, Valentina; Zhang, Yongzhen

(Nature Publishing Group, 2019)

TY  - JOUR
AU  - Li, Kun
AU  - Stanojević, Maja
AU  - Stamenković, Gorana
AU  - Ilić, Bojan
AU  - Paunović, Milan
AU  - Lu, Miao
AU  - Pešić, Branislav
AU  - Đurić Maslovara, Ivana
AU  - Siljic, Marina
AU  - Cirkovic, Valentina
AU  - Zhang, Yongzhen
PY  - 2019
UR  - http://www.nature.com/articles/s41598-019-55077-y
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6904564
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3575
AB  - Rickettsiales bacteria in arthropods play a significant role in both public health and arthropod ecology. However, the extensive genetic diversity of Rickettsiales endosymbionts of arthropods is still to be discovered. In 2016, 515 arthropods belonging to 9 species of four classes (Insecta, Chilopoda, Diplopoda and Arachnida) were collected in Serbia. The presence and genetic diversity of Rickettsiales bacteria were evaluated by characterizing the 16S rRNA (rrs), citrate synthase (gltA) and heat shock protein (groEL) genes. The presence of various Rickettsiales bacteria was identified in the majority of tested arthropod species. The results revealed co-circulation of five recognized Rickettsiales species including Rickettsia, Ehrlichia and Wolbachia, as well as four tentative novel species, including one tentative novel genus named Neowolbachia. These results suggest the remarkable genetic diversity of Rickettsiales bacteria in certain arthropod species in this region. Furthermore, the high prevalence of spotted fever group Rickettsia in Ixodes ricinus ticks highlights the potential public health risk of human Rickettsia infection.
PB  - Nature Publishing Group
T2  - Scientific Reports
T1  - Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.
IS  - 1
VL  - 9
DO  - 10.1038/s41598-019-55077-y
SP  - 18680
ER  - 
@article{
author = "Li, Kun and Stanojević, Maja and Stamenković, Gorana and Ilić, Bojan and Paunović, Milan and Lu, Miao and Pešić, Branislav and Đurić Maslovara, Ivana and Siljic, Marina and Cirkovic, Valentina and Zhang, Yongzhen",
year = "2019",
abstract = "Rickettsiales bacteria in arthropods play a significant role in both public health and arthropod ecology. However, the extensive genetic diversity of Rickettsiales endosymbionts of arthropods is still to be discovered. In 2016, 515 arthropods belonging to 9 species of four classes (Insecta, Chilopoda, Diplopoda and Arachnida) were collected in Serbia. The presence and genetic diversity of Rickettsiales bacteria were evaluated by characterizing the 16S rRNA (rrs), citrate synthase (gltA) and heat shock protein (groEL) genes. The presence of various Rickettsiales bacteria was identified in the majority of tested arthropod species. The results revealed co-circulation of five recognized Rickettsiales species including Rickettsia, Ehrlichia and Wolbachia, as well as four tentative novel species, including one tentative novel genus named Neowolbachia. These results suggest the remarkable genetic diversity of Rickettsiales bacteria in certain arthropod species in this region. Furthermore, the high prevalence of spotted fever group Rickettsia in Ixodes ricinus ticks highlights the potential public health risk of human Rickettsia infection.",
publisher = "Nature Publishing Group",
journal = "Scientific Reports",
title = "Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.",
number = "1",
volume = "9",
doi = "10.1038/s41598-019-55077-y",
pages = "18680"
}
Li, K., Stanojević, M., Stamenković, G., Ilić, B., Paunović, M., Lu, M., Pešić, B., Đurić Maslovara, I., Siljic, M., Cirkovic, V.,& Zhang, Y.. (2019). Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.. in Scientific Reports
Nature Publishing Group., 9(1), 18680.
https://doi.org/10.1038/s41598-019-55077-y
Li K, Stanojević M, Stamenković G, Ilić B, Paunović M, Lu M, Pešić B, Đurić Maslovara I, Siljic M, Cirkovic V, Zhang Y. Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.. in Scientific Reports. 2019;9(1):18680.
doi:10.1038/s41598-019-55077-y .
Li, Kun, Stanojević, Maja, Stamenković, Gorana, Ilić, Bojan, Paunović, Milan, Lu, Miao, Pešić, Branislav, Đurić Maslovara, Ivana, Siljic, Marina, Cirkovic, Valentina, Zhang, Yongzhen, "Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia." in Scientific Reports, 9, no. 1 (2019):18680,
https://doi.org/10.1038/s41598-019-55077-y . .
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Failure to detect viral RNA in bat samples collected in the Balkan region

Ćirković, Valentina; Stamenković, Gorana; Jovanović, Jelena; Šiljić, Marina; Paunović, Milan; Stanojević, Maja

(2016)

TY  - JOUR
AU  - Ćirković, Valentina
AU  - Stamenković, Gorana
AU  - Jovanović, Jelena
AU  - Šiljić, Marina
AU  - Paunović, Milan
AU  - Stanojević, Maja
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2547
AB  - Bats represent a known reservoir of emerging viruses, yet no molecular data are found about the occurrence of zoonotic viruses in bats in the Balkans. The aim of this study was to determine the presence of paramyxo- and hanta-viruses in bats, examined by PCR in 95 deceased bats, that were collected in Serbia and Montenegro, during the period 2002 to 2009. All samples tested positive for beta-actin mRNA, confirming successful RNA isolation and amplification. However, no sample tested positive for virus specific RNA. Our findings might reflect tissue degradation in carcass samples and do not exclude bats as potential viral reservoir in the surveyed geographic area.
T2  - Tropical Biomedicine
T1  - Failure to detect viral RNA in bat samples collected in the Balkan region
IS  - 4
VL  - 33
SP  - 780
EP  - 785
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2547
ER  - 
@article{
author = "Ćirković, Valentina and Stamenković, Gorana and Jovanović, Jelena and Šiljić, Marina and Paunović, Milan and Stanojević, Maja",
year = "2016",
abstract = "Bats represent a known reservoir of emerging viruses, yet no molecular data are found about the occurrence of zoonotic viruses in bats in the Balkans. The aim of this study was to determine the presence of paramyxo- and hanta-viruses in bats, examined by PCR in 95 deceased bats, that were collected in Serbia and Montenegro, during the period 2002 to 2009. All samples tested positive for beta-actin mRNA, confirming successful RNA isolation and amplification. However, no sample tested positive for virus specific RNA. Our findings might reflect tissue degradation in carcass samples and do not exclude bats as potential viral reservoir in the surveyed geographic area.",
journal = "Tropical Biomedicine",
title = "Failure to detect viral RNA in bat samples collected in the Balkan region",
number = "4",
volume = "33",
pages = "780-785",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2547"
}
Ćirković, V., Stamenković, G., Jovanović, J., Šiljić, M., Paunović, M.,& Stanojević, M.. (2016). Failure to detect viral RNA in bat samples collected in the Balkan region. in Tropical Biomedicine, 33(4), 780-785.
https://hdl.handle.net/21.15107/rcub_ibiss_2547
Ćirković V, Stamenković G, Jovanović J, Šiljić M, Paunović M, Stanojević M. Failure to detect viral RNA in bat samples collected in the Balkan region. in Tropical Biomedicine. 2016;33(4):780-785.
https://hdl.handle.net/21.15107/rcub_ibiss_2547 .
Ćirković, Valentina, Stamenković, Gorana, Jovanović, Jelena, Šiljić, Marina, Paunović, Milan, Stanojević, Maja, "Failure to detect viral RNA in bat samples collected in the Balkan region" in Tropical Biomedicine, 33, no. 4 (2016):780-785,
https://hdl.handle.net/21.15107/rcub_ibiss_2547 .
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Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly Detected Focus in the Balkan Peninsula

Stamenković, Gorana; Nikolic, V.; Blagojević, Jelena; Bugarski-Stanojević, Vanja; Adnađević, Tanja; Stanojevic, M.; Vujošević, Mladen

(2015)

TY  - JOUR
AU  - Stamenković, Gorana
AU  - Nikolic, V.
AU  - Blagojević, Jelena
AU  - Bugarski-Stanojević, Vanja
AU  - Adnađević, Tanja
AU  - Stanojevic, M.
AU  - Vujošević, Mladen
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1999
AB  - Dobrava-Belgrade virus (DOBV) is a hantavirus species that causes the
   most severe form of haemorrhagic fever with renal syndrome (HFRS) in
   Europe. DOBV has been detected in three Apodemus rodents: A.flavicollis,
   A.agrarius and A.ponticus. These emerging viruses appear throughout the
   Balkan Peninsula including Serbia as its central part. In this study, we
   examined the seroprevalence, molecular epidemiology and phylogenetics of
   DOBV from A.flavicollis captured at six Serbian localities. Furthermore,
   we applied microsatellite typing of host animal genome to analyse the
   role of host kinship in DOBV animal transmission. The overall IgG
   seropositivity rate over 3years (2008-2010) was 11.9\% (22/185). All
   seropositive samples were subjected to RT-PCR and DNA sequencing for S
   and L genome segments (pos. 291-1079nt and 2999-3316nt, respectively).
   DOBV was genetically detected in three samples from mountain Tara in
   western Serbia, a newly detected DOBV focus in the Balkans. No sequence
   data from human cases from Serbia are available for the studied period.
   However, collected DOBV isolates in this work phylogenetically clustered
   together with isolates from Serbian human cases dating from 2002, with
   1.9\% nucleotide divergence. We determined the level of kinship between
   seropositive and seronegative animal groups and found no significant
   difference, suggesting that horizontal virus transmission in the studied
   population was the same within and among the hatches. Our findings are
   the first genetic detection of DOBV in rodents in Serbia. We confirm
   wide and continuous hantavirus presence in the examined parts of the
   Balkans, underlying the necessity of continual monitoring of hantavirus
   circulation in A.flavicollis.
T2  - Zoonoses and Public Health
T1  - Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly
 Detected Focus in the Balkan Peninsula
IS  - 2
VL  - 62
DO  - 10.1111/zph.12136
SP  - 141
EP  - 150
ER  - 
@article{
author = "Stamenković, Gorana and Nikolic, V. and Blagojević, Jelena and Bugarski-Stanojević, Vanja and Adnađević, Tanja and Stanojevic, M. and Vujošević, Mladen",
year = "2015",
abstract = "Dobrava-Belgrade virus (DOBV) is a hantavirus species that causes the
   most severe form of haemorrhagic fever with renal syndrome (HFRS) in
   Europe. DOBV has been detected in three Apodemus rodents: A.flavicollis,
   A.agrarius and A.ponticus. These emerging viruses appear throughout the
   Balkan Peninsula including Serbia as its central part. In this study, we
   examined the seroprevalence, molecular epidemiology and phylogenetics of
   DOBV from A.flavicollis captured at six Serbian localities. Furthermore,
   we applied microsatellite typing of host animal genome to analyse the
   role of host kinship in DOBV animal transmission. The overall IgG
   seropositivity rate over 3years (2008-2010) was 11.9\% (22/185). All
   seropositive samples were subjected to RT-PCR and DNA sequencing for S
   and L genome segments (pos. 291-1079nt and 2999-3316nt, respectively).
   DOBV was genetically detected in three samples from mountain Tara in
   western Serbia, a newly detected DOBV focus in the Balkans. No sequence
   data from human cases from Serbia are available for the studied period.
   However, collected DOBV isolates in this work phylogenetically clustered
   together with isolates from Serbian human cases dating from 2002, with
   1.9\% nucleotide divergence. We determined the level of kinship between
   seropositive and seronegative animal groups and found no significant
   difference, suggesting that horizontal virus transmission in the studied
   population was the same within and among the hatches. Our findings are
   the first genetic detection of DOBV in rodents in Serbia. We confirm
   wide and continuous hantavirus presence in the examined parts of the
   Balkans, underlying the necessity of continual monitoring of hantavirus
   circulation in A.flavicollis.",
journal = "Zoonoses and Public Health",
title = "Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly
 Detected Focus in the Balkan Peninsula",
number = "2",
volume = "62",
doi = "10.1111/zph.12136",
pages = "141-150"
}
Stamenković, G., Nikolic, V., Blagojević, J., Bugarski-Stanojević, V., Adnađević, T., Stanojevic, M.,& Vujošević, M.. (2015). Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly
 Detected Focus in the Balkan Peninsula. in Zoonoses and Public Health, 62(2), 141-150.
https://doi.org/10.1111/zph.12136
Stamenković G, Nikolic V, Blagojević J, Bugarski-Stanojević V, Adnađević T, Stanojevic M, Vujošević M. Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly
 Detected Focus in the Balkan Peninsula. in Zoonoses and Public Health. 2015;62(2):141-150.
doi:10.1111/zph.12136 .
Stamenković, Gorana, Nikolic, V., Blagojević, Jelena, Bugarski-Stanojević, Vanja, Adnađević, Tanja, Stanojevic, M., Vujošević, Mladen, "Genetic Analysis of Dobrava-Belgrade Virus from Western Serbia - A Newly
 Detected Focus in the Balkan Peninsula" in Zoonoses and Public Health, 62, no. 2 (2015):141-150,
https://doi.org/10.1111/zph.12136 . .
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The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death

Tovilović-Kovačević, Gordana; Ristić, Biljana; Milenković, Marina; Stanojević, Maja; Trajković, Vladimir

(John Wiley & Sons, Inc., 2014)

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana
AU  - Milenković, Marina
AU  - Stanojević, Maja
AU  - Trajković, Vladimir
PY  - 2014
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6346
AB  - Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus- and cell-type-dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy-dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time- and cell-type-dependent fine-tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.
PB  - John Wiley & Sons, Inc.
T2  - Medicinal Research Reviews
T1  - The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death
IS  - 4
VL  - 34
DO  - 10.1002/med.21303
SP  - 744
EP  - 767
ER  - 
@article{
author = "Tovilović-Kovačević, Gordana and Ristić, Biljana and Milenković, Marina and Stanojević, Maja and Trajković, Vladimir",
year = "2014",
abstract = "Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus- and cell-type-dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy-dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time- and cell-type-dependent fine-tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.",
publisher = "John Wiley & Sons, Inc.",
journal = "Medicinal Research Reviews",
title = "The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death",
number = "4",
volume = "34",
doi = "10.1002/med.21303",
pages = "744-767"
}
Tovilović-Kovačević, G., Ristić, B., Milenković, M., Stanojević, M.,& Trajković, V.. (2014). The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death. in Medicinal Research Reviews
John Wiley & Sons, Inc.., 34(4), 744-767.
https://doi.org/10.1002/med.21303
Tovilović-Kovačević G, Ristić B, Milenković M, Stanojević M, Trajković V. The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death. in Medicinal Research Reviews. 2014;34(4):744-767.
doi:10.1002/med.21303 .
Tovilović-Kovačević, Gordana, Ristić, Biljana, Milenković, Marina, Stanojević, Maja, Trajković, Vladimir, "The Role and Therapeutic Potential of Autophagy Modulation in Controlling Virus-Induced Cell Death" in Medicinal Research Reviews, 34, no. 4 (2014):744-767,
https://doi.org/10.1002/med.21303 . .
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mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells

Tovilović-Kovačević, Gordana; Ristić, Biljana; Šiljić, Marina; Nikolić, Valentina; Kravić-Stevović, Tamara; Dulović, Marija; Milenković, Marina; Knežević, Aleksandra; Bošnjak, Mihajlo; Bumbaširević, Vladimir; Stanojević, Maja; Trajković, Vladimir

(Elsevier Masson SAS, 2013)

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana
AU  - Šiljić, Marina
AU  - Nikolić, Valentina
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Milenković, Marina
AU  - Knežević, Aleksandra
AU  - Bošnjak, Mihajlo
AU  - Bumbaširević, Vladimir
AU  - Stanojević, Maja
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6345
AB  - We investigated the role of autophagy, a stress-inducible lysosomal self-digestion of cellular components, in modulation of herpes simplex virus type 1 (HSV-1)-triggered death of U251 human glioma cells. HSV-1 caused apoptotic death in U251 cells, characterized by phosphatidylserine externalization, caspase activation and DNA fragmentation. HSV-1-induced apoptosis was associated with the induction of autophagic response, as confirmed by the conversion of cytosolic LC3-I to autophagosome-associated LC3-II, increase in intracellular acidification, presence of autophagic vesicles, and increase in proteolysis of the selective autophagic target p62. HSV-1-triggered autophagy was not associated with the significant increase in the expression of proautophagic protein beclin-1 or downregulation of the major autophagy suppressor mammalian target of rapamycin (mTOR). Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK-activated protein kinase (AMPK) were accordingly activated and suppressed, respectively. An shRNA-mediated knockdown of the autophagy-essential LC3b, as well as pharmacological inhibition of autophagy with bafilomycin A1 or 3-methyladenine, markedly accelerated apoptotic changes and ensuing cell death in HSV-1-infected glioma cells. These data indicate that AMPK/Akt/mTOR-independent autophagy could prolong survival of HSV-1-infected U251 glioma cells by counteracting the coinciding apoptotic response.
PB  - Elsevier Masson SAS
T2  - Microbes and Infection
T1  - mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells
IS  - 8-9
VL  - 15
DO  - 10.1016/j.micinf.2013.04.012
SP  - 615
EP  - 624
ER  - 
@article{
author = "Tovilović-Kovačević, Gordana and Ristić, Biljana and Šiljić, Marina and Nikolić, Valentina and Kravić-Stevović, Tamara and Dulović, Marija and Milenković, Marina and Knežević, Aleksandra and Bošnjak, Mihajlo and Bumbaširević, Vladimir and Stanojević, Maja and Trajković, Vladimir",
year = "2013",
abstract = "We investigated the role of autophagy, a stress-inducible lysosomal self-digestion of cellular components, in modulation of herpes simplex virus type 1 (HSV-1)-triggered death of U251 human glioma cells. HSV-1 caused apoptotic death in U251 cells, characterized by phosphatidylserine externalization, caspase activation and DNA fragmentation. HSV-1-induced apoptosis was associated with the induction of autophagic response, as confirmed by the conversion of cytosolic LC3-I to autophagosome-associated LC3-II, increase in intracellular acidification, presence of autophagic vesicles, and increase in proteolysis of the selective autophagic target p62. HSV-1-triggered autophagy was not associated with the significant increase in the expression of proautophagic protein beclin-1 or downregulation of the major autophagy suppressor mammalian target of rapamycin (mTOR). Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK-activated protein kinase (AMPK) were accordingly activated and suppressed, respectively. An shRNA-mediated knockdown of the autophagy-essential LC3b, as well as pharmacological inhibition of autophagy with bafilomycin A1 or 3-methyladenine, markedly accelerated apoptotic changes and ensuing cell death in HSV-1-infected glioma cells. These data indicate that AMPK/Akt/mTOR-independent autophagy could prolong survival of HSV-1-infected U251 glioma cells by counteracting the coinciding apoptotic response.",
publisher = "Elsevier Masson SAS",
journal = "Microbes and Infection",
title = "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells",
number = "8-9",
volume = "15",
doi = "10.1016/j.micinf.2013.04.012",
pages = "615-624"
}
Tovilović-Kovačević, G., Ristić, B., Šiljić, M., Nikolić, V., Kravić-Stevović, T., Dulović, M., Milenković, M., Knežević, A., Bošnjak, M., Bumbaširević, V., Stanojević, M.,& Trajković, V.. (2013). mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection
Elsevier Masson SAS., 15(8-9), 615-624.
https://doi.org/10.1016/j.micinf.2013.04.012
Tovilović-Kovačević G, Ristić B, Šiljić M, Nikolić V, Kravić-Stevović T, Dulović M, Milenković M, Knežević A, Bošnjak M, Bumbaširević V, Stanojević M, Trajković V. mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection. 2013;15(8-9):615-624.
doi:10.1016/j.micinf.2013.04.012 .
Tovilović-Kovačević, Gordana, Ristić, Biljana, Šiljić, Marina, Nikolić, Valentina, Kravić-Stevović, Tamara, Dulović, Marija, Milenković, Marina, Knežević, Aleksandra, Bošnjak, Mihajlo, Bumbaširević, Vladimir, Stanojević, Maja, Trajković, Vladimir, "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells" in Microbes and Infection, 15, no. 8-9 (2013):615-624,
https://doi.org/10.1016/j.micinf.2013.04.012 . .
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