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Differential Localization of Structural and Non-Structural Proteins during the Bluetongue Virus Replication Cycle

Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway

Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland
Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Sciences, Jagiellonian University, Lojasiewicza 11, 30-348 Krakow, Poland
Department of Cardiac Surgery and Transplantology, Silesian Center for Heart Diseases, Marii Curie-Skłodowskiej 9, 41-800 Zabrze, Poland
Faculty of Chemistry, Jagiellonian University, 30-387 Krakow, Poland
Author to whom correspondence should be addressed.
Viruses 2020, 12(3), 344;
Received: 12 February 2020 / Revised: 15 March 2020 / Accepted: 18 March 2020 / Published: 21 March 2020
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
Background: Berberine (BBR) is an isoquinoline alkaloid which exhibits a variety of biological and therapeutic properties, and has been reported by some to block replication of the influenza virus. However, contradictory results have also been presented, and the mechanistic explanation is lacking. Methods: A panel of cell lines (Madin–Darby canine kidney (MDCK), adenocarcinoma human alveolar basal epithelial cells (A549), lung epithelial type I (LET1)) and primary human airway epithelial cells (HAE) susceptible to influenza virus infection were infected with a seasonal influenza A virus in the presence or absence of BBR. Cytotoxicity towards cell lines was measured using XTT assay. The yield of the virus was analyzed using RT-qPCR. To study the molecular mechanism of BBR, confocal microscopy and Western blot analyses of cellular fractions were applied. Results and conclusions: Our results show cell-type-dependent anti-influenza properties of BBR in vitro which suggests that the compound acts on the cell and not the virus. Importantly, BBR hampers influenza replication in primary human airway epithelium 3D cultures that mimic the natural replication site of the virus. Studies show that the influenza A virus upregulates the mitogen-activated protein kinase/extracellular signal-related kinase (MAPK/ERK) pathway and hijacks this pathway for nucleolar export of the viral ribonucleoprotein. Our results suggest that BBR interferes with this process and hampers influenza A replication. View Full-Text
Keywords: influenza; berberine; MAPK pathway influenza; berberine; MAPK pathway
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MDPI and ACS Style

Botwina, P.; Owczarek, K.; Rajfur, Z.; Ochman, M.; Urlik, M.; Nowakowska, M.; Szczubiałka, K.; Pyrc, K. Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway. Viruses 2020, 12, 344.

AMA Style

Botwina P, Owczarek K, Rajfur Z, Ochman M, Urlik M, Nowakowska M, Szczubiałka K, Pyrc K. Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway. Viruses. 2020; 12(3):344.

Chicago/Turabian Style

Botwina, Paweł, Katarzyna Owczarek, Zenon Rajfur, Marek Ochman, Maciej Urlik, Maria Nowakowska, Krzysztof Szczubiałka, and Krzysztof Pyrc. 2020. "Berberine Hampers Influenza A Replication through Inhibition of MAPK/ERK Pathway" Viruses 12, no. 3: 344.

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