Low Molecular Weight Sulfated Chitosan Efficiently Reduces Infection Capacity of Porcine Circovirus Type 2 (PCV2) In PK15 Cells

2021 ◽  
Author(s):  
Daniela Jiménez-Arriagada ◽  
Alejandro A. Hidalgo ◽  
Victor Neira ◽  
Andrónico Neira-Carrillo ◽  
Sergio A. Bucarey
Keyword(s):  
Molecular Weight ◽  
Antiviral Activity ◽  
Mode Of Action ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Porcine Circovirus ◽  
Molecular Weights ◽  
Associated Diseases

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 could act as a 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 copy number upon application different molecular weights, sulfate functionalization, and concentration of polymer. In addition, to explore the mode of action of the Chi-S against PCV2 infection, experiments were designed to clarify 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 of PCV2, showing specific antiviral effects depending on its molecular weight, concentration, and chemical functionalization. Assays designed to explore the mode of action of Chi-S revealed that exerted antiviral activity through impeding viral attachment and penetration into cells. Conclusions These findings help better understanding PCV2-porcine cells interaction and reinforce the idea that sulfated polymers, such as Chi-S, represent a promising candidate for uses in antiviral therapies against PCV2-associated diseases.

scholarly journals Porcine Circovirus Type 2 Rep Enhances IL-10 Production in Macrophages via Activation of p38-MAPK Pathway

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1141
Author(s):  
Xingchen Wu ◽  
Xiaoya Wang ◽  
Tengfei Shi ◽  
Le Luo ◽  
Dan Qiao ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Porcine Circovirus ◽  
Rep Proteins ◽  
Il10 Promoter ◽  
Later Phase

Porcine circovirus type 2 (PCV2) is one of the major threats to pig farms worldwide. Although PCV2 has been identified to promote IL-10 production, the detailed regulatory roles of PCV2 Rep for IL-10 production remain unclear. Herein, we first found that PCV2 Rep, rather than PCV1 Rep, enhanced IL-10 expression at the later phase of PCV2 infection in porcine alveolar macrophages (PAMs). Furthermore, we found that PCV2 Rep directly activated the p38-MAPK pathway to promote transcription factors NF-κB p50 and Sp1 binding to the il10 promoter, but PCV1 Rep did not. During PCV2 infection, however, PCV2 Rep promoted the binding activities of NF-κB p50 and Sp1 with the il10 promoter only at the later phase of PCV2 infection, since Rep proteins only expressed at the later phase of the infection. Moreover, silence of the thymine DNA glycosylase (TDG), a Rep-binding protein, significantly reduced the binding activities of NF-κB p50 and Sp1 with il10 promoter, resulting in the reduction of IL-10 production in PCV2-inoculated PAMs at the later phase of infection. Taken together, our results demonstrate that Rep proteins enhance IL-10 production during PCV2 infection of PAMs via activation of p38-MAPK pathways, in which host TDG is a critical mediator.

scholarly journals Strain-Dependent Porcine Circovirus Type 2 (PCV2) Entry and Replication in T-Lymphoblasts

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 813 ◽  
Author(s):  
Wei ◽  
Van Renne ◽  
Nauwynck
Keyword(s):  
Nucleic Acid ◽  
Serine Proteases ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Productive Infection ◽  
Porcine Circovirus ◽  
Progeny Virus ◽  
T Lymphoblasts

Porcine circovirus type 2 (PCV2) is the etiological agent of PCV2-associated diseases (PCVAD). PCV2 targets lymphoblasts, and pigs suffering from PCVAD display lymphocyte depletion in lymphoid tissues. PCV2 infection of lymphoblasts has not been studied. Here, the replication cycle of PCV2 (abortion strain 1121 and PMWS strain Stoon1010) in T-lymphoblasts was examined. The expression of Rep and Cap were found for both viral strains, while progeny virus was detected for Stoon1010 but not for 1121. PCV2 attached to 11–26% (1121-Stoon1010) of the T-lymphoblasts while 2.6–12.7% of cells showed virus internalization. Chondroitin sulfate (CS) was present on 25% of T-lymphoblasts, and colocalized with PCV2 on 31–32% of the PCV2+ cells. Enzymatic removal of CS reduced PCV2 infection. PCV2 infection was decreased by chlorpromazine, cytochalasin D and Clostridium difficile toxin B for both viral strains and by amiloride for 1121 but not for Stoon1010. Inhibiting either endosome acidification or serine proteases strongly reduced PCV2 infection. Three-dimensional analysis of Cap structure demonstrated a better Cap-nucleic acid affinity for Stoon1010 than for 1121. Taken together, PCV2 binds to T-lymphoblasts partially via CS, enters via clathrin-mediated endocytosis, and disassembles under functions of a pH-drop and serine proteases. Strain Stoon1010 displayed an enhanced viral binding, a specific receptor-mediated endocytosis, an increased Cap-nucleic acid affinity, and a more productive infection in T-lymphoblasts than 1121 did, indicating an evolution from 1121 to Stoon1010.

scholarly journals Porcine Circovirus Type 2 Infection Decreases the Efficacy of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus Vaccine

2006 ◽  
Vol 13 (8) ◽  
pp. 923-929 ◽  
Author(s):  
T. Opriessnig ◽  
N. E. McKeown ◽  
K. L. Harmon ◽  
X. J. Meng ◽  
P. G. Halbur
Keyword(s):  
Age Groups ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Daily Weight Gain ◽  
Porcine Circovirus ◽  
Respiratory Syndrome Virus ◽  
Live Virus ◽  
Lymphoid Depletion

ABSTRACT Porcine reproductive and respiratory syndrome virus (PRRSV)-induced pneumonia is a major problem, and vaccination is used to reduce losses associated with PRRSV. Porcine circovirus type 2 (PCV2) causes lymphoid depletion, and there is concern that this adversely affects the immune response. The objective of this study was to investigate the effect of PCV2 infection on the efficacy of modified live virus (MLV) PRRSV vaccine. Sixty-nine 2-week-old pigs were randomly assigned to one of seven groups of 9 to 10 pigs each. At 6 weeks of age, pigs in groups 4, 5, and 6 were inoculated intranasally with PCV2 ISU-40895. At 8 weeks of age, groups 3, 4, 6, and 7 were vaccinated with a PRRSV MLV vaccine. At 12 weeks of age, groups 2, 3, and 4 were challenged with PRRSV SDSU73. All pigs were necropsied 14 days after PRRSV challenge. PCV2-infected, PRRSV-vaccinated, and PRRSV-challenged pigs had significantly (P < 0.05) more-severe macroscopic lung lesions than did the PRRSV-vaccinated and PRRSV-challenged pigs that were not exposed to PCV2 prior to PRRSV vaccination. Nonvaccinated PRRSV-infected pigs had a significantly (P < 0.001) higher incidence of PRRSV antigen in lungs than did all other groups except the group infected with PCV2 prior to PRRSV vaccination and challenge. The nonvaccinated PRRSV-challenged group and the group challenged with PCV2 prior to PRRSV vaccination and challenge had significantly (P < 0.001) lower average daily weight gain than did the control and the vaccinated groups. This work suggests that PCV2 infection has an adverse effect on the development of protective immunity induced by PRRSV vaccine.

scholarly journals Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection

2021 ◽  
Vol 12 ◽  
Author(s):  
Wen Zhang ◽  
Zhendong Fu ◽  
Hongyan Yin ◽  
Qingbing Han ◽  
Wenhui Fan ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Pcv2 Infection ◽  
Porcine Circovirus ◽  
Economic Losses ◽  
Target Cells ◽  
M2 Macrophage ◽  
Bacterial Coinfection

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus–associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset of M1-associated genes and M2-associated genes. Mechanistically, induction of M1-associated genes by PCV2 infection is dependent on activation of nuclear factor kappa B (NF-κB) and c-jun N-terminal kinase (JNK) signaling pathways whereas suppression of M2-associated genes by PCV2 is via inhibiting expression of jumonji domain containing-3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase that regulates M2 activation of macrophages. Finally, we identified that PCV2 capsid protein (Cap) directly inhibits JMJD3 transcription to restrain expression of interferon regulatory factor (IRF4) that controls M2 macrophage polarization. Consequently, sustained infection of PCV2 facilitates bacterial infection in vitro. In summary, these findings showed that PCV2 infection functionally modulated M1 macrophage polarization via targeting canonical signals and epigenetic histone modification, which contributes to bacterial coinfection and virial pathogenesis.

scholarly journals Detection and molecular characterization of porcine circovirus type 2 from piglets with Porcine Circovirus Associated Diseases in Colombia

2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Antonia Rincón Monroy ◽  
Gloria Consuelo Ramirez-Nieto ◽  
Victor Julio Vera ◽  
Jairo Jaime Correa ◽  
Jose Dario Mogollón-Galvis
Keyword(s):  
Molecular Characterization ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Associated Diseases

Porcine circovirus type 2 and associated diseases in Romania — Short communication

2007 ◽  
Vol 55 (1) ◽  
pp. 151-156 ◽  
Author(s):  
D. Cadar ◽  
A. Cságola ◽  
Á. Dán ◽  
Z. Deim ◽  
Marina Spînu ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Porcine Circovirus Type ◽  
Postweaning Multisystemic Wasting Syndrome ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Serum Samples ◽  
Associated Diseases ◽  
Wasting Syndrome

Porcine circovirus type 2 (PCV2) has been demonstrated to be the causal agent for postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). This report describes the first detection of PCV2 and associated diseases in a Romanian swine herd located in Transylvania. The clinical signs, pathological and histopathological changes observed in affected pigs were similar to those previously described for PDNS and PMWS. Polymerase chain reaction and in situ hybridisation were used for the detection of PCV2 nucleic acids from tissues and serum samples. Complete PCV2 genomes of both PMWS and PDNS cases were sequenced and analysed, and by comparing them with each other no genomic differences could be detected. The sequence analysis showed that the Romanian PCV2 was closely related to PCV2 identified in France and in Hungary.

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