Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals
Abstract
:1. Introduction
2. Results
2.1. Detection and Quantification of MCPyV DNA in Urine and Plasma Samples by Quantitative Real-Time Polymerase Chain Reaction (qPCR) Analysis
2.2. Nucleotide Analysis of MCPyV VP1
2.3. Amino-Acid and Structural Analysis of MCPyV VP1
2.4. In Vitro Results: Replication Efficiency
2.5. In Vitro Results: Immunofluorescence Staining
2.6. In Vitro Results: VP1 Amplification, Analysis and Sequencing
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. MCPyV DNA Extraction and Quantification by qPCR
4.3. Sample Selection and VP1 Amplification, Analysis, and Sequencing
4.4. VP1 Amino-Acid Translation and Analysis
4.5. In Vitro Cells Cultures: Transfection, Infection, and Evaluation of the Replication Efficiency
4.6. In Vitro Cells Cultures: Immunofluorescence Staining
4.7. In Vitro Cells Cultures: Analysis and Sequencing of MCPyV VP1
4.8. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Ethical Approval
Abbreviations
MCPyV | Merkel Cell Polyomavirus |
T | Tumor |
LT | Large T |
sT | small T |
ALTO | LT open reading frame |
VP1 | viral protein 1 |
VP2 | viral protein 2 |
ATG | adenine-thymine-guanine |
HPyVs | human polyomaviruses |
NCCR | non-coding control region |
ORI | origin of replication |
NLS | nuclear localization signal |
VLPs | virus-like particles |
MCC | Merkel cell carcinoma |
qPCR | quantitative Real-Time polymerase chain reaction |
IF | immunofluorescence |
SPNTs | supernatants |
I | insertion |
∆ | deletion |
d.p.t. | days post-transfection |
d.p.i. | days post infection |
PBS | phosphate-buffered saline |
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Variants | PROVEAN Score; Effects | DynaMut; Effects |
---|---|---|
Asp69Val | −1.994; neutral | ΔΔG: 0.506 kcal/mol; stabilizing |
Ser251Phe | −1.459; neutral | ΔΔG: 1.431 kcal/mol; stabilizing |
Ile115Phe | −1.809; neutral | ΔΔG: 1.371 kcal/mol; stabilizing |
Thr47Ser | −2.586; deleterious | ΔΔG: −0.442 kcal/mol; destabilizing |
Tyr79∆ | −4.793; deleterious |
1st Round of Infection | |||
MCPyV Variant | 3 d.p.i. | 7 d.p.i. | Increase (%) * |
MCC350 | 1.5 × 103 # | 1.75 × 103 | 17 |
7U | 0.5 × 103 | 0.92 × 103 | 84 |
12U | - | - | - |
12P | - | - | - |
11P | - | - | - |
17P | - | - | - |
17U | 1 × 103 | 1.2 × 103 | 20 |
7P | 0.1 × 103 | 0.12 × 103 | 20 |
2nd round of infection | |||
MCC350 | 2 × 103 | 3.5 × 103 | 75 |
7U | 0.85 × 103 | 1.5 × 103 | 76 |
12U | - | - | - |
12P | - | - | - |
11P | - | - | - |
17P | - | - | - |
17U | 5.8 × 103 | 9 × 103 | 55 |
7P | 0.6 × 103 | 1 × 103 | 67 |
Patients Enrolled | Total n. | Gender, n. | Age | HIV-1 RNA Load, Range | CD4+ Counts, Range |
---|---|---|---|---|---|
Naive | 40 | Male: 30; Female: 10 | Range: 21–68 y.o. Mean: 39.27 y.o. | 1.26 × 103–10 × 106 copies/ml | 9–890/mm3 |
Experienced | 60 | Male: 46; Female: 14 | Range: 21–76 y.o. Mean: 43.7 y.o. | TND *-27 × 105 copies/ml | 312–1178/mm3 |
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Prezioso, C.; Bianchi, M.; Obregon, F.; Ciotti, M.; Sarmati, L.; Andreoni, M.; Palamara, A.T.; Pascarella, S.; Moens, U.; Pietropaolo, V. Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. Int. J. Mol. Sci. 2020, 21, 7998. https://doi.org/10.3390/ijms21217998
Prezioso C, Bianchi M, Obregon F, Ciotti M, Sarmati L, Andreoni M, Palamara AT, Pascarella S, Moens U, Pietropaolo V. Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals. International Journal of Molecular Sciences. 2020; 21(21):7998. https://doi.org/10.3390/ijms21217998
Chicago/Turabian StylePrezioso, Carla, Martina Bianchi, Francisco Obregon, Marco Ciotti, Loredana Sarmati, Massimo Andreoni, Anna Teresa Palamara, Stefano Pascarella, Ugo Moens, and Valeria Pietropaolo. 2020. "Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals" International Journal of Molecular Sciences 21, no. 21: 7998. https://doi.org/10.3390/ijms21217998