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Your search keyword '"Dondalska, Aleksandra"' showing total 2 results
Start Over Author "Dondalska, Aleksandra" Publisher kth, genteknologi
2 results on '"Dondalska, Aleksandra"'

1. Single-Stranded Oligonucleotide-Mediated Inhibition of Respiratory Syncytial Virus Infection

Author

Pålsson, Sandra Axberg, Dondalska, Aleksandra, Bergenstråhle, Joseph, Rolfes, Caroline, Björk, Albin, Sedano, Laura, Power, Ultan F., Rameix-Welti, Marie-Anne, Lundeberg, Joakim, Wahren-Herlenius, Marie, Mastrangelo, Peter, Eleouet, Jean-Francois, Le Goffic, Ronan, Galloux, Marie, Spetz, Anna-Lena, Pålsson, Sandra Axberg, Dondalska, Aleksandra, Bergenstråhle, Joseph, Rolfes, Caroline, Björk, Albin, Sedano, Laura, Power, Ultan F., Rameix-Welti, Marie-Anne, Lundeberg, Joakim, Wahren-Herlenius, Marie, Mastrangelo, Peter, Eleouet, Jean-Francois, Le Goffic, Ronan, Galloux, Marie, and Spetz, Anna-Lena

Abstract

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children. Currently, there is no RSV vaccine or universally accessible antiviral treatment available. Addressing the urgent need for new antiviral agents, we have investigated the capacity of a non-coding single-stranded oligonucleotide (ssON) to inhibit RSV infection. By utilizing a GFP-expressing RSV, we demonstrate that the ssON significantly reduced the proportion of RSV infected A549 cells (lung epithelial cells). Furthermore, we show that ssON's antiviral activity was length dependent and that both RNA and DNA of this class of oligonucleotides have antiviral activity. We reveal that ssON inhibited RSV infection by competing with the virus for binding to the cellular receptor nucleolin in vitro. Additionally, using a recombinant RSV that expresses luciferase we show that ssON effectively blocked RSV infection in mice. Treatment with ssON in vivo resulted in the upregulation of RSV-induced interferon stimulated genes (ISGs) such as Stat1, Stat2, Cxcl10, and Ccl2. This study highlights the possibility of using oligonucleotides as therapeutic agents against RSV infection. We demonstrate that the mechanism of action of ssON is the inhibition of viral entry in vitro, likely through the binding of the receptor, nucleolin and that ssON treatment against RSV infection in vivo additionally results in the upregulation of ISGs., QC 20210120

Published
2020
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2. A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A (H1N1) Infection

Author

Poux, Candice, Dondalska, Aleksandra, Bergenstråhle, Joseph, Pålsson, Sandra, Contreras, Vanessa, Arasa, Claudia, Järver, Peter, Albert, Jan, Busse, David, LeGrand, Roger, Lundeberg, Joakim, Tregoning, John, Spetz, Anna-Lena, Commission of the European Communities, and Wellcome Trust

Subjects
Science & Technology, mice, Immunology, single-stranded oligonucleotides, Immunology in the medical area, INNATE, IMMUNITY, co-stimulatory molecules, clathrin-mediated endocytosis, BARRIER, DENDRITIC CELLS, cytokines, Microbiology in the medical area, RIG-I, PROTEASES, 1107 Immunology, Immunologi inom det medicinska området, Immunologi, Mikrobiologi inom det medicinska området, VIRUS, human monocyte-derived dendritic cells (MoDC), TLR3, influenza A, Life Sciences & Biomedicine, RESPONSES
Abstract

The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssON's capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation. Exogenous TLR3 stimulation did not overcome the IAV-mediated inhibition of co-stimulatory molecule expression in MoDC. However, TLR3 stimulation using PolyI:C led to an augmented pro-inflammatory cytokine response. We reveal that ssON effectively inhibited PolyI:C-mediated pro-inflammatory cytokine production in MoDC, notably, ssON treatment maintained an interferon response induced by IAV infection. Accordingly, RNAseq analyses revealed robust up-regulation of interferon-stimulated genes in IAV cultures treated with ssON. We next measured reduced IAV production in MoDC treated with ssON and found a length requirement for its anti-viral activity, which overlapped with its capacity to inhibit uptake of PolyI:C. Hence, in cases wherein an overreacting TLR3 activation contributes to IAV pathogenesis, ssON can reduce this signaling pathway. Furthermore, concomitant treatment with ssON and IAV infection in mice resulted in maintained weight and reduced viral load in the lungs. Therefore, extracellular ssON provides a mechanism for immune regulation of TLR3-mediated responses and suppression of IAV infection in vitro and in vivo in mice. QC 20210126

Published
2019

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