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Article ; Online: Feline herpesvirus 1 (FHV-1) enters the cell by receptor-mediated endocytosis.

Synowiec, Aleksandra / Dąbrowska, Agnieszka / Pachota, Magdalena / Baouche, Meriem / Owczarek, Katarzyna / Niżański, Wojciech / Pyrc, Krzysztof

Journal of virology

2023 Volume 97, Issue 8, Page(s) e0068123

Abstract: Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to ... ...

Abstract	Feline herpesvirus type 1 (FHV-1) is an enveloped dsDNA virus belonging to the
MeSH term(s)	Animals ; Cats ; Cat Diseases/virology ; Caveolin 1/metabolism ; Clathrin/metabolism ; Endocytosis ; Herpesviridae Infections/veterinary ; RNA, Small Interfering/genetics ; Varicellovirus/metabolism
Chemical Substances	Caveolin 1 ; Clathrin ; RNA, Small Interfering
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00681-23
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Article ; Online: Kijowski Majdan jako symbol nowej Ukrainy

Aleksandra Synowiec

Studia Etnologiczne i Antropologiczne, Vol

2015 Volume 15

Keywords	Ethnology. Social and cultural anthropology ; GN301-674
Language	Czech
Publishing date	2015-02-01T00:00:00Z
Publisher	University of Silesia Press
Document type	Article ; Online
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Article ; Online: An engineered A549 cell line expressing CD13 and TMPRSS2 is permissive to clinical isolate of human coronavirus 229E.

Lie, Laurensius Kevin / Synowiec, Aleksandra / Mazur, Jedrzej / Rabalski, Lukasz / Pyrć, Krzysztof

Virology

2023 Volume 588, Page(s) 109889

Abstract: The lack of suitable in vitro culture model has hampered research on wild-type (WT) human coronaviruses. While 3D tissue or organ cultures have been instrumental for this purpose, such models are challenging, time-consuming, expensive and require ... ...

Abstract	The lack of suitable in vitro culture model has hampered research on wild-type (WT) human coronaviruses. While 3D tissue or organ cultures have been instrumental for this purpose, such models are challenging, time-consuming, expensive and require extensive cell culture adaptation and directed evolution. Consequently, high-throughput applications are beyond reach in most cases. Here we developed a robust A549 cell line permissive to a human coronavirus 229E (HCoV-229E) clinical isolate by transducing CD13 and transmembrane serine protease 2 (TMPRSS2), henceforth referred to as A549
MeSH term(s)	Humans ; Coronavirus 229E, Human/genetics ; A549 Cells ; Cathepsins/metabolism ; Endocytosis ; Coronavirus Infections ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism
Chemical Substances	Cathepsins (EC 3.4.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2023.109889
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Article ; Online: An engineered A549 cell line expressing CD13 and TMPRSS2 is permissive to clinical isolate of human coronavirus 229E

Lie, Laurensius Kevin / Synowiec, Aleksandra / Mazur, Jedrzej / Pyrc, Krzysztof

bioRxiv

Abstract: Many viruses are well adapted to in vivo conditions but perform poorly in vitro, requiring extensive cell culture adaptation and directed evolution. Coronaviruses are indifferent, and the lack of suitable in vitro culture models delayed or hampered ... ...

Abstract	Many viruses are well adapted to in vivo conditions but perform poorly in vitro, requiring extensive cell culture adaptation and directed evolution. Coronaviruses are indifferent, and the lack of suitable in vitro culture models delayed or hampered research on wild-type (WT) human coronaviruses for years. While 3D tissue or organ cultures have been instrumental for this purpose, such models are challenging, time-consuming, expensive, and require advanced cell culture expertise. Consequently, high-throughput applications are beyond reach in most cases. Here we developed a robust A549 cell line permissive to human coronavirus 229E (HCoV-229E) clinical isolates by transducing CD13 and transmembrane serine protease 2 (TMPRSS2), henceforth referred to as A549++ cells. This modification allowed for productive infection and resulted in syncytia formation in infected A549++ cells. Moreover, a more detailed analysis showed that the virus might use the TMPRSS2-dependent pathway but can still bypass this pathway using the cathepsin-mediated, endocytosis-dependent route. Overall, our data showed that A549++ cells are permissive to HCoV-229E clinical isolate and can be used for antiviral drug screening and further studies on HCoV-229E clinical isolate infection biology. Moreover, this line constitutes a uniform platform for studies on multiple members of the Coronaviridae family.
Keywords	covid19
Language	English
Publishing date	2023-07-21
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.07.21.545505
Database	COVID19

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Article ; Online: Polyploidy formation in cancer cells: How a Trojan horse is born.

Was, Halina / Borkowska, Agata / Olszewska, Aleksandra / Klemba, Aleksandra / Marciniak, Marta / Synowiec, Agnieszka / Kieda, Claudine

Seminars in cancer biology

2021 Volume 81, Page(s) 24–36

Abstract: Ploidy increase has been shown to occur in different type of tumors and participate in tumor initiation and resistance to the treatment. Polyploid giant cancer cells (PGCCs) are cells with multiple nuclei or a single giant nucleus containing multiple ... ...

Abstract	Ploidy increase has been shown to occur in different type of tumors and participate in tumor initiation and resistance to the treatment. Polyploid giant cancer cells (PGCCs) are cells with multiple nuclei or a single giant nucleus containing multiple complete sets of chromosomes. The mechanism leading to formation of PGCCs may depend on: endoreplication, mitotic slippage, cytokinesis failure, cell fusion or cell cannibalism. Polyploidy formation might be triggered in response to various genotoxic stresses including: chemotherapeutics, radiation, hypoxia, oxidative stress or environmental factors like: air pollution, UV light or hyperthermia. A fundamental feature of polyploid cancer cells is the generation of progeny during the reversal of the polyploid state (depolyploidization) that may show high aggressiveness resulting in the formation of resistant disease and tumor recurrence. Therefore, we propose that modern anti-cancer therapies should be designed taking under consideration polyploidization/ depolyploidization processes, which confer the polyploidization a hidden potential similar to a Trojan horse delayed aggressiveness. Various mechanisms and stress factors leading to polyploidy formation in cancer cells are discussed in this review.
MeSH term(s)	Cell Nucleus ; Giant Cells ; Humans ; Neoplasm Recurrence, Local/pathology ; Polyploidy
Language	English
Publishing date	2021-03-13
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2021.03.003
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Article ; Online: Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells: A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy.

Synowiec, Agnieszka / Brodaczewska, Klaudia / Wcisło, Gabriel / Majewska, Aleksandra / Borkowska, Agata / Filipiak-Duliban, Aleksandra / Gawrylak, Aleksandra / Wilkus, Kinga / Piwocka, Katarzyna / Kominek, Agata / Waś, Halina / Lewicki, Sławomir / Siewiera, Jacek / Szczylik, Cezary / Szenajch, Jolanta / Kubiak, Jacek Z / Kieda, Claudine

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined ... ...

Abstract	Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO
MeSH term(s)	Humans ; Female ; Cisplatin/pharmacology ; Cisplatin/therapeutic use ; Ovarian Neoplasms/metabolism ; Resveratrol/pharmacology ; Vascular Endothelial Growth Factor A/metabolism ; Cell Line, Tumor ; Hypoxia ; Vascular Endothelial Growth Factors/metabolism ; Cell Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Tumor Microenvironment
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Resveratrol (Q369O8926L) ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2023-03-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065715
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Article ; Online: Hypoxia, but Not Normoxia, Reduces Effects of Resveratrol on Cisplatin Treatment in A2780 Ovarian Cancer Cells

Agnieszka Synowiec / Klaudia Brodaczewska / Gabriel Wcisło / Aleksandra Majewska / Agata Borkowska / Aleksandra Filipiak-Duliban / Aleksandra Gawrylak / Kinga Wilkus / Katarzyna Piwocka / Agata Kominek / Halina Waś / Sławomir Lewicki / Jacek Siewiera / Cezary Szczylik / Jolanta Szenajch / Jacek Z. Kubiak / Claudine Kieda

International Journal of Molecular Sciences, Vol 24, Iss 5715, p

A Challenge for Resveratrol Use in Anticancer Adjuvant Cisplatin Therapy

2023 Volume 5715

Abstract	Natural compounds, such as resveratrol (Res), are currently used as adjuvants for anticancer therapies. To evaluate the effectiveness of Res for the treatment of ovarian cancer (OC), we screened the response of various OC cell lines to the combined treatment with cisplatin (CisPt) and Res. We identified A2780 cells as the most synergistically responding, thus optimal for further analysis. Because hypoxia is the hallmark of the solid tumor microenvironment, we compared the effects of Res alone and in combination with CisPt in hypoxia (pO 2 = 1%) vs. normoxia (pO 2 = 19%). Hypoxia caused an increase (43.2 vs. 5.0%) in apoptosis and necrosis (14.2 vs. 2.5%), reactive oxygen species production, pro-angiogenic HIF-1α (hypoxia-inducible factor-1α) and VEGF (vascular endothelial growth factor), cell migration, and downregulated the expression of ZO1 (zonula occludens-1) protein in comparison to normoxia. Res was not cytotoxic under hypoxia in contrast to normoxia. In normoxia, Res alone or CisPt+Res caused apoptosis via caspase-3 cleavage and BAX, while in hypoxia, it reduced the accumulation of A2780 cells in the G2/M phase. CisPt+Res increased levels of vimentin under normoxia and upregulated SNAI1 expression under hypoxia. Thus, various effects of Res or CisPt+Res on A2780 cells observed in normoxia are eliminated or diminished in hypoxia. These findings indicate the limitations in using Res as an adjuvant with CisPt therapy in OC.
Keywords	ovarian cancer ; cisplatin ; resveratrol ; normoxia ; hypoxia ; epithelial–mesenchymal transition markers ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection.

Synowiec, Aleksandra / Szczepański, Artur / Barreto-Duran, Emilia / Lie, Laurensius Kevin / Pyrc, Krzysztof

Clinical microbiology reviews

2021 Volume 34, Issue 2

Abstract: To date, seven identified coronaviruses (CoVs) have been found to infect humans; of these, three highly pathogenic variants have emerged in the 21st century. The newest member of this group, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ... ...

Abstract	To date, seven identified coronaviruses (CoVs) have been found to infect humans; of these, three highly pathogenic variants have emerged in the 21st century. The newest member of this group, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected at the end of 2019 in Hubei province, China. Since then, this novel coronavirus has spread worldwide, causing a pandemic; the respiratory disease caused by the virus is called coronavirus disease 2019 (COVID-19). The clinical presentation ranges from asymptomatic to mild respiratory tract infections and influenza-like illness to severe disease with accompanying lung injury, multiorgan failure, and death. Although the lungs are believed to be the site at which SARS-CoV-2 replicates, infected patients often report other symptoms, suggesting the involvement of the gastrointestinal tract, heart, cardiovascular system, kidneys, and other organs; therefore, the following question arises: is COVID-19 a respiratory or systemic disease? This review aims to summarize existing data on the replication of SARS-CoV-2 in different tissues in both patients and
MeSH term(s)	COVID-19/epidemiology ; COVID-19/physiopathology ; China/epidemiology ; Humans ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Pandemics ; Respiratory Tract Infections/epidemiology ; Respiratory Tract Infections/physiopathology ; SARS-CoV-2/pathogenicity
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645015-5
ISSN	1098-6618 ; 0893-8512
ISSN (online)	1098-6618
ISSN	0893-8512
DOI	10.1128/CMR.00133-20
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Article ; Online: Reversible rearrangement of the cellular cytoskeleton: A key to the broad-spectrum antiviral activity of novel amphiphilic polymers.

Dabrowska, Agnieszka / Botwina, Pawel / Barreto-Duran, Emilia / Kubisiak, Agata / Obloza, Magdalena / Synowiec, Aleksandra / Szczepanski, Artur / Targosz-Korecka, Marta / Szczubialka, Krzysztof / Nowakowska, Maria / Pyrc, Krzysztof

Materials today. Bio

2023 Volume 22, Page(s) 100763

Abstract: The battle against emerging viral infections has been uneven, as there is currently no broad-spectrum drug available to contain the spread of novel pathogens throughout the population. Consequently, the pandemic outbreak that occurred in early 2020 laid ... ...

Abstract	The battle against emerging viral infections has been uneven, as there is currently no broad-spectrum drug available to contain the spread of novel pathogens throughout the population. Consequently, the pandemic outbreak that occurred in early 2020 laid bare the almost empty state of the pandemic box. Therefore, the development of novel treatments with broad specificity has become a paramount concern in this post-pandemic era. Here, we propose copolymers of poly (sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and poly (sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS
Language	English
Publishing date	2023-08-07
Publishing country	England
Document type	Journal Article
ISSN	2590-0064
ISSN (online)	2590-0064
DOI	10.1016/j.mtbio.2023.100763
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Article ; Online: Novel inhibitors of HSV-1 protease effective in vitro and in vivo.

Pachota, Magdalena / Grzywa, Renata / Iwanejko, Jakub / Synowiec, Aleksandra / Iwan, Dominika / Kamińska, Karolina / Skoreński, Marcin / Bielecka, Ewa / Szczubiałka, Krzysztof / Nowakowska, Maria / Mackereth, Cameron D / Wojaczyńska, Elżbieta / Sieńczyk, Marcin / Pyrć, Krzysztof

Antiviral research

2023 Volume 213, Page(s) 105604

Abstract: Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with ... ...

Abstract	Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy.
MeSH term(s)	Humans ; Herpesvirus 1, Human ; Peptide Hydrolases ; Antiviral Agents/therapeutic use ; Acyclovir/pharmacology ; Herpes Simplex/drug therapy ; Drug Resistance, Viral
Chemical Substances	Peptide Hydrolases (EC 3.4.-) ; Antiviral Agents ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2023-04-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105604
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