Strain-Dependent Porcine Circovirus Type 2 (PCV2) Entry and Replication in T-Lymphoblasts
Abstract
:1. Introduction
2. Materials and Methods
2.1. Generation of Porcine T-Lymphoblasts In Vitro
2.2. Virus Preparation and Particle Quantification
2.3. PCV2 Peplication Kinetics in T-Lymphoblasts
2.4. PCV2 Attachment to T-Lymphoblasts
2.4.1. Visualization of PCV2 Attachment
2.4.2. Determination of the Expression of GAGs on T-Lymphoblasts
2.4.3. Evaluation of PCV2 Particles Binding to CS-Expressed T-Lymphoblasts
2.4.4. Effect of Enzymatic Treatment on PCV2 Infection in T-Lymphoblasts
2.5. PCV2 Entry and Disassembly in T-Lymphoblasts
2.5.1. Visualization of PCV2 Internalization
2.5.2. Effect of Different Entry Inhibitors on PCV2 Infection in T-Lymphoblasts
2.5.3. Effect of Acidotropic Agents on PCV2 Infection in T-Lymphoblasts
2.5.4. Effect of AEBSF on PCV2 Infection in T-Lymphoblasts
2.6. Toxicity Assays
2.7. Amino Acid and 3D Structural Analyses of PCV2 Cap Sequences from Strains 1121 and Stoon1010
2.8. Statistical Analysis
3. Results
3.1. The In Vitro Generated T-Lymphoblasts Support PCV2 Replication
3.2. PCV2 Attachment to T-Lymphoblasts is Mediated by Chondroitin Sulfate
3.2.1. PCV2 Attachment is Restricted to 11–26% of T-Lymphoblasts
3.2.2. CS, but Not Other GAGs, is Expressed on T-Lymphoblasts
3.2.3. PCV2 Particles Were Able to Bind to T-Lymphoblasts With and Without CS Molecules
3.2.4. Enzymatic Removal of CS Decreased PCV2 Infection of T-Lymphoblasts
3.3. PCV2 Entry and Disassembly in T-Lymphoblasts
3.3.1. Visualization of PCV2 Internalization
3.3.2. PCV2 Strain 1121, but Not Stoon1010, Exploits Macropinocytosis for Its Entry
3.3.3. PCV2 Entry Occurs via Clathrin-Mediated Endocytosis and is Independent of Caveolae-Mediated Endocytosis
3.3.4. PCV2 Entry Into T-Lymphoblasts Requires Actin
3.3.5. Participation of Small GTPases in PCV2 Entry into T-Lymphoblasts
3.3.6. PCV2 Infection of T-Lymphoblasts Requires a Low-pH Step
3.3.7. PCV2 Disassembly is Mediated by Serine Proteases
3.4. Structural Difference of PCV2 Cap between Strains 1121 and Stoon1010
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AEBSF | 4-(2-aminoethyl) benzenesulfonyl fluoride |
ATCC | American Type Culture Collection |
Cap | capsid protein |
CHO | Chinese hamster ovary |
ConA | concanavalin A |
CS | chondroitin sulfate |
DABCO | 1,4-diazobicyclo-2.2.2-octane |
DPBS | Dulbecco’s PBS |
DSHB | the Developmental Studies Hybridoma Bank |
FCS | fetal calf serum |
GAG | glycosaminoglycan |
HA | hyaluronic acid |
HIV | human immunodeficiency virus |
HS | heparan sulfate |
HSV | herpes simplex virus |
IL-2 | interleukin-2 |
IPMA | immunoperoxidase monolayer assay |
I-TASSER | iterative threading assembly refinement |
JEV | Japanese encephalitis virus |
KS | keratan sulfate |
mAb | monoclonal antibody |
mβCD | methyl-β-cyclodextrin |
MTT | metabolize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
ORF | open reading frame |
PBMC | porcine blood mononuclear cell |
PCV | porcine circovirus |
PCVAD | PCV2-associated disease |
PF | paraformaldehyde |
PMWS | postweaning multisystemic wasting syndrome |
Rep | replicase protein |
RT | room temperature |
SK | swine kidney |
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Wei, R.; Van Renne, N.; Nauwynck, H.J. Strain-Dependent Porcine Circovirus Type 2 (PCV2) Entry and Replication in T-Lymphoblasts. Viruses 2019, 11, 813. https://doi.org/10.3390/v11090813
Wei R, Van Renne N, Nauwynck HJ. Strain-Dependent Porcine Circovirus Type 2 (PCV2) Entry and Replication in T-Lymphoblasts. Viruses. 2019; 11(9):813. https://doi.org/10.3390/v11090813
Chicago/Turabian StyleWei, Ruifang, Nicolaas Van Renne, and Hans J. Nauwynck. 2019. "Strain-Dependent Porcine Circovirus Type 2 (PCV2) Entry and Replication in T-Lymphoblasts" Viruses 11, no. 9: 813. https://doi.org/10.3390/v11090813