Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Viral Titers
2.2. Detection of MCMV MiRNAs In Vitro
2.3. Examination of MCMV MiRNAs in Different Animal Models
2.4. Transfection and Quantification of Viral Loads for MiRNAs in Group 1
2.5. Transfection and Quantification of Viral Loads for MiRNAs in Group 2
2.6. Effects of Agomir Administration on MCMV Recurrence
2.7. Immunohistochemistry
2.8. Statistical Analysis
3. Results
3.1. MCMV MiRNAExpression during Lytic Infection In Vitro
3.2. In Vivo MiRNA Expression Profiles Differ from In Vitro Profiles
3.3. The Inhibition of Group 1 Viral MiRNAs Exerts Few Effectson MCMV Replication In Vitro
3.4. The Overexpression of Several Viral miRNAs in Group 2 Inhibits MCMV Production In Vitro
3.5. MCMV MiRNA Agomirs Reduce MCMV Recurrence In Vivo
4. Discussion
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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MiRNA Name | Accession Number | Melting Temperature (°C) | Primer F (5′–3′) | Primer R (5′–3′) | Group |
---|---|---|---|---|---|
miR-m01-1 | MIMAT0005533 | 71.5 | GCAGAGAGGAGAATAACGTC | GTCCAGTTTTTTTTTTTTTTTCCGT | 2 |
miR-m01-2-5p | MIMAT0005534 | 72 | CAGGAAGAGAATCGGGTTG | GTCCAGTTTTTTTTTTTTTTTACCGT | 1 |
miR-m01-2-3p | MIMAT0005535 | 72.5 | GCGTTCGACACGGTTTCC | GTCCAGTTTTTTTTTTTTTTTCGAAG | 1 |
miR-m01-3-5p | MIMAT0005536 | 74 | AGCGGTGAAGCGACTGTTGC | GTCCAGTTTTTTTTTTTTTTTCGAG | 2 |
miR-m01-3-3p | MIMAT0005537 | 75 | AGCGAGGAACGCTCGCTTCAC | GGTCCAGTTTTTTTTTTTTTTTGCC | 2 |
miR-m01-4-5p | MIMAT0005538 | 75 | CGCAGTCCTATGCTAACAC | GGTCCAGTTTTTTTTTTTTTTTCAC | 1 |
miR-m01-4-3p | MIMAT0005539 | 74 | AGCGCCGCGTGGTAGCAT | GGTCCAGTTTTTTTTTTTTTTTGTTCT | 2 |
miR-m21-1 | MIMAT0005540 | 72.5 | GCAGATAGGGGACACGTTC | CAGTTTTTTTTTTTTTTTCGGCTTG | 1 |
miR-m22-1 | MIMAT0005541 | 73.5 | CAGTTCCCGTCCGTACCGA | CCAGTTTTTTTTTTTTTTTGGCCT | 2 |
miR-M23-1-5p | MIMAT0005542 | 73 | ACTCGGTACGGACGGGGAA | GTCCAGTTTTTTTTTTTTTTTACGGT | 2 |
miR-M23-1-3p | MIMAT0005543 | 75 | CTCCTGCGTCGGCCCGAG | GTCCAGTTTTTTTTTTTTTTTGGC | 2 |
miR-M23-2-5p | MIMAT0005544 | 73 | CAGTGAACGTGTCCCCTATC | GGTCCAGTTTTTTTTTTTTTTTCCA | 1 |
miR-M23-2-3p | MIMAT0005545 | 74.5 | AGCAGATGGGGGCCTCGGT | AGTTTTTTTTTTTTTTTCCGCTTGA | 1 |
miR-M44-1 | MIMAT0005546 | 74 | CGCAGTATCTTTTTCCAGAG | AGGTCCAGTTTTTTTTTTTTTTTACC | 1 |
miR-M55-1 | MIMAT0005547 | 75.5 | GGTGATCGGCGTGCTA | GTCCAGTTTTTTTTTTTTTTTACGG | 2 |
miR-m59-1 | MIMAT0005548 | 73.5 | TTAGCAGTGCCTCGACCGT | GGTCCAGTTTTTTTTTTTTTTTCTGA | 2 |
miR-m59-2 | MIMAT0005549 | 73.5 | GCCCGAAGAGCCCTC | AGTTTTTTTTTTTTTTTGGCTCTGT | 2 |
miR-M87-1 | MIMAT0005550 | 74.5 | CCGTCGGCAGCG | GGTCCAGTTTTTTTTTTTTTTTGCT | 2 |
miR-m88-1-5p | MIMAT0005551 | 73 | CAGATGACCGACCCCCTGA | CCAGTTTTTTTTTTTTTTTCCGATGT | 2 |
miR-m88-1-3p | MIMAT0005552 | 74 | AGCAGCAGAAGTCGATGT | GTCCAGTTTTTTTTTTTTTTTAGACC | 1 |
miR-M95-1-5p | MIMAT0005553 | 73.5 | AGGGTCGTGGGCTTGTGT | CAGTTTTTTTTTTTTTTTCAAGCGA | 1 |
miR-M95-1-3p | MIMAT0005554 | 75 | AGCGACGTCGGACCGCGA | CCAGTTTTTTTTTTTTTTTGCCGT | 2 |
miR-m107-1-5p | MIMAT0005555 | 75.5 | CGGTCACTCGTCTCGA | CCAGTTTTTTTTTTTTTTTGGTGACT | 2 |
miR-m107-1-3p | MIMAT0005556 | 75.5 | AGTGCTCGCGTCGAGTGACC | GGTCCAGTTTTTTTTTTTTTTTGAG | 2 |
miR-m108-1-5p | MIMAT0005557 | 73 | CAGTCACGAGCAACCGCCC | TCCAGTTTTTTTTTTTTTTTCATTTC | 2 |
miR-m108-1-3p | MIMAT0005558 | 74 | CAGTTTCTGACGGTGGCT | GTCCAGTTTTTTTTTTTTTTTCGAC | 2 |
miR-m108-2-5p.1 | MIMAT0005560 | 75 | GGCGGTCACTCGAC | AGTTTTTTTTTTTTTTTCGGTGCT | 2 |
miR-m108-2-5p.2 | MIMAT0005559 | 74 | TCACTCGTCGCGAGCGGT | GGTCCAGTTTTTTTTTTTTTTTGTGA | 1 |
miR-m108-2-3p | MIMAT0005561 | 73.5 | GTGACTCGAGACGAGTGA | GGTCCAGTTTTTTTTTTTTTTTACCG | 1 |
Acute Infection Group (N = 15), n (%) | Viral Reactivation Group (N = 17), n (%) | |||||
---|---|---|---|---|---|---|
Livers | Lungs | Blood | Livers | Lungs | Blood | |
miR-m01-1 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
miR-m01-2-5p | 15 (100) | 15 (100) | 15 (100) | 17 (100) | 17 (100) | 15 (88) |
miR-m01-2-3p | 15 (100) | 15 (100) | 3 (20) | 17 (100) | 14 (82) | 1 (6) |
miR-m01-3-5p | 0 (0) | 3 (20) | 1 (7) | 0 (0) | 0 (0) | 0 (0) |
miR-m01-3-3p | 0 (0) | 1 (7) | 0 (0) | 0 (0) | 0 (0) | 1 (6) |
miR-m01-4-5p | 15 (100) | 15 (100) | 9 (60) | 17 (100) | 17 (100) | 7 (41) |
miR-m01-4-3p | 3 (20) | 0 (0) | 4 (27) | 3 (18) | 0 (0) | 3 (18) |
miR-m21-1 | 15 (100) | 15 (100) | 6 (40) | 17 (100) | 17 (100) | 9 (53) |
miR-m22-1 | 6 (40) | 3 (20) | 3 (20) | 3 (18) | 3 (18) | 2 (12) |
miR-M23-1-5p | 2 (13) | 1 (7) | 0 (0) | 3 (18) | 0 (0) | 1 (6) |
miR-M23-1-3p | 0 (0) | 0 (0) | 1 (7) | 0 (0) | 2 (12) | 0 (0) |
miR-M23-2-5p | 14 (93) | 15 (100) | 8 (53) | 12 (71) | 14 (82) | 9 (53) |
miR-M23-2-3p | 15 (100) | 15 (100) | 8 (53) | 17 (100) | 14 (82) | 13 (76) |
miR-M44-1 | 15 (100) | 12 (80) | 2 (13) | 17 (100) | 14 (82) | 4 (24) |
miR-M55-1 | 1 (7) | 1 (7) | 0 (0) | 0 (0) | 0 (0) | 2 (12) |
miR-m59-1 | 0 (0) | 0 (0) | 1 (7) | 2 (12) | 0 (0) | 0 (0) |
miR-m59-2 | 3 (20) | 0 (0) | 0 (0) | 0 (0) | 3 (18) | 1 (6) |
miR-M87-1 | 0 (0) | 2 (13) | 1 (7) | 0 (0) | 0 (0) | 0 (0) |
miR-m88-1-5p | 1 (7) | 0 (0) | 0 (0) | 0 (0) | 3 (18) | 0 (0) |
miR-m88-1-3p | 15 (100) | 15 (100) | 8 (53) | 17 (100) | 17 (100) | 12 (71) |
miR-M95-1-5p | 15 (100) | 15 (100) | 3 (20) | 17 (100) | 17 (100) | 7 (41) |
miR-M95-1-3p | 0 (0) | 2 (13) | 0 (0) | 0 (0) | 2 (12) | 2 (12) |
miR-m107-1-5p | 3 (20) | 0 (0) | 1 (7) | 0 (0) | 0 (0) | 1 (6) |
miR-m107-1-3p | 0 (0) | 1 (7) | 3 (20) | 0 (0) | 0 (0) | 0 (0) |
miR-m108-1-5p | 3 (20) | 0 (0) | 0 (0) | 2 (12) | 2 (12) | 0 (0) |
miR-m108-1-3p | 3 (20) | 2 (13) | 4 (27) | 1 (6) | 1 (6) | 1 (6) |
miR-m108-2-5p.1 | 2 (13) | 3 (20) | 1 (7) | 0 (0) | 0 (0) | 0 (0) |
miR-m108-2-5p.2 | 12 (80) | 9 (60) | 10 (67) | 17 (100) | 12 (71) | 11 (65) |
miR-m108-2-3p | 12 (80) | 15 (100) | 7 (47) | 17 (100) | 17 (100) | 15 (88) |
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Deng, J.; Xiao, J.; Ma, P.; Gao, B.; Gong, F.; Lv, L.; Zhang, Y.; Xu, J. Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection. Viruses 2017, 9, 118. https://doi.org/10.3390/v9050118
Deng J, Xiao J, Ma P, Gao B, Gong F, Lv L, Zhang Y, Xu J. Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection. Viruses. 2017; 9(5):118. https://doi.org/10.3390/v9050118
Chicago/Turabian StyleDeng, Jiang, Jun Xiao, Ping Ma, Bo Gao, Feng Gong, Liping Lv, Yanyu Zhang, and Jinbo Xu. 2017. "Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection" Viruses 9, no. 5: 118. https://doi.org/10.3390/v9050118