Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells

Abstract Background Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to vaccines, the availability of antiviral polymers provides an efficient and safe option for reducing the impact of these diseases. By virtue of their molecular...

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Main Authors: Daniela Jiménez-Arriagada, Alejandro A. Hidalgo, Victor Neira, Andrónico Neira-Carrillo, Sergio A. Bucarey
Format: Article
Language:English
Published: BMC 2022-03-01
Series:Virology Journal
Subjects:
Online Access:https://doi.org/10.1186/s12985-022-01781-7
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author Daniela Jiménez-Arriagada
Alejandro A. Hidalgo
Victor Neira
Andrónico Neira-Carrillo
Sergio A. Bucarey
author_facet Daniela Jiménez-Arriagada
Alejandro A. Hidalgo
Victor Neira
Andrónico Neira-Carrillo
Sergio A. Bucarey
author_sort Daniela Jiménez-Arriagada
collection DOAJ
description Abstract Background Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to vaccines, the availability of antiviral polymers provides an efficient and safe option for reducing the impact of these diseases. By virtue of their molecular weight and repetitious structure, polymers possess properties not found in small-molecule drugs. In this perspective, we focus on chitosan, a ubiquitous biopolymer, that adjusts the molecular weight and sulfated-mediated functionality can act as an efficient antiviral polymer by mimicking PCV2-cell receptor interactions. Methods Sulfated chitosan (Chi-S) polymers of two molecular weights were synthesized and characterized by FTIR, SEM–EDS and elemental analysis. The Chi-S solutions were tested against PCV2 infection in PK15 cells in vitro and antiviral activity was evaluated by measuring the PCV2 DNA copy number, TCID50 and capsid protein expression, upon application of different molecular weights, sulfate functionalization, and concentrations of polymer. In addition, to explore the mode of action of the Chi-S against PCV2 infection, experiments were designed to elucidate whether the antiviral activity of the Chi-S would be influenced by when it was added to the cells, relative to the time and stage of viral infection. Results Chi-S significantly reduced genomic copies, TCID50 titers and capsid protein of PCV2, showing specific antiviral effects depending on its molecular weight, concentration, and chemical functionalization. Assays designed to explore the mode of action of the low molecular weight Chi-S revealed that it exerted antiviral activity through impeding viral attachment and penetration into cells. Conclusions These findings help better understanding the interactions of PCV2 and porcine cells and reinforce the idea that sulfated polymers, such as Chi-S, represent a promising candidates for use in antiviral therapies against PCV2-associated diseases. Further studies in swine are warranted.
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spelling doaj.art-24887f295482479d9d8c8a0a58658d4d2022-12-22T02:39:40ZengBMCVirology Journal1743-422X2022-03-0119111310.1186/s12985-022-01781-7Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cellsDaniela Jiménez-Arriagada0Alejandro A. Hidalgo1Victor Neira2Andrónico Neira-Carrillo3Sergio A. Bucarey4Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias, Campus Sur Universidad de ChileEscuela de Química y Farmacia, Facultad de Medicina, Universidad Andres BelloUnidad de Virología, Departamento de Medicina Preventiva, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de ChileLaboratorio Polyform, Departamento de Ciencias Biológicas, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de ChileDepartamento de Ciencias Biológicas, Centro Biotecnológico Veterinario, Biovetec, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de ChileAbstract Background Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to vaccines, the availability of antiviral polymers provides an efficient and safe option for reducing the impact of these diseases. By virtue of their molecular weight and repetitious structure, polymers possess properties not found in small-molecule drugs. In this perspective, we focus on chitosan, a ubiquitous biopolymer, that adjusts the molecular weight and sulfated-mediated functionality can act as an efficient antiviral polymer by mimicking PCV2-cell receptor interactions. Methods Sulfated chitosan (Chi-S) polymers of two molecular weights were synthesized and characterized by FTIR, SEM–EDS and elemental analysis. The Chi-S solutions were tested against PCV2 infection in PK15 cells in vitro and antiviral activity was evaluated by measuring the PCV2 DNA copy number, TCID50 and capsid protein expression, upon application of different molecular weights, sulfate functionalization, and concentrations of polymer. In addition, to explore the mode of action of the Chi-S against PCV2 infection, experiments were designed to elucidate whether the antiviral activity of the Chi-S would be influenced by when it was added to the cells, relative to the time and stage of viral infection. Results Chi-S significantly reduced genomic copies, TCID50 titers and capsid protein of PCV2, showing specific antiviral effects depending on its molecular weight, concentration, and chemical functionalization. Assays designed to explore the mode of action of the low molecular weight Chi-S revealed that it exerted antiviral activity through impeding viral attachment and penetration into cells. Conclusions These findings help better understanding the interactions of PCV2 and porcine cells and reinforce the idea that sulfated polymers, such as Chi-S, represent a promising candidates for use in antiviral therapies against PCV2-associated diseases. Further studies in swine are warranted.https://doi.org/10.1186/s12985-022-01781-7ChitosanAntiviral polymersSulfated chitosanPorcine circovirus type 2PK15 cellsCell attachment
spellingShingle Daniela Jiménez-Arriagada
Alejandro A. Hidalgo
Victor Neira
Andrónico Neira-Carrillo
Sergio A. Bucarey
Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
Virology Journal
Chitosan
Antiviral polymers
Sulfated chitosan
Porcine circovirus type 2
PK15 cells
Cell attachment
title Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
title_full Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
title_fullStr Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
title_full_unstemmed Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
title_short Low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 (PCV2) in PK15 cells
title_sort low molecular weight sulfated chitosan efficiently reduces infection capacity of porcine circovirus type 2 pcv2 in pk15 cells
topic Chitosan
Antiviral polymers
Sulfated chitosan
Porcine circovirus type 2
PK15 cells
Cell attachment
url https://doi.org/10.1186/s12985-022-01781-7
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