Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump
Abstract
:1. Introduction
2. Materials and Methods
2.1. Compounds
2.2. Viruses
2.3. Cell Culture, Virus Infection, and Antiviral Assays
2.4. Cytotoxicity Assay
2.5. Quantitative Reverse Transcriptase PCR (qRT-PCR)
2.6. SDS-Polyacrylamide Gel Electrophoresis and Immunoblot Analysis
2.7. Cellular Localization of α3
2.8. NLS Analysis of the α3 Isoform
2.9. Immunofluorescence Assay
2.10. Nuclear Coimmunoprecipitation and Immunoblotting
2.11. Statistical Analysis
3. Results
3.1. α3 mRNA Is Induced in GPCMV and HCMV-Infected Cells but Not in MCMV-Infected Cells
3.2. Inhibition of GPCMV Replication with Digitoxin Correlates with Reduced α3 Expression
3.3. Levels of α3 mRNA and Protein Are Reduced in HCMV-Infected Digitoxin-Treated Cells
3.4. Concentration-Dependent Decrease in α3 Expression in HCMV-Infected HFFs Treated with Digitoxin Analogs
3.5. α3 Is Localized in the Nuclear Compartment and Interacts with PML and IE1 During Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Primer Sequence |
---|---|
Human α1—Fwd | 5′-CCAAGCTGCTACAGAAGAGGAACC-3′ |
Human α1—Rev | 5′-TTGAAGGATTCCATGATCTTTGAAC-3′ |
Human α2—Fwd | 5′-CGCTCGACAAGGAGATGCAAGA-3′ |
Human α2—Rev | 5′-CCGAGGAAACTTTCCAGATGGC-3′ |
Human α3—Fwd | 5′-TTC GGG GGC TTC TCC ATC CT-3′ |
Human α3—Rev | 5’-GCA CTC GGT CTC CAC CCT TGA-3’ |
Mouse α1—Fwd | 5’-CCGTGGATAACCTCTGCTTCGT-3’ |
Mouse α1—Rev | 5’-CGCTGTGATTGGATGGTCTCCT-3’ |
Mouse α2—Fwd | 5’-CTGTCCTTGGATGAGCTGGGC-3’ |
Mouse α2—Rev | 5’-ACTTGACCCACTCAGGAGTTGTGG-3’ |
Mouse α3—Fwd | 5’-GGTGTGGGTATCATCTCTGAGG-3’ |
Mouse α3—Rev | 5’-CGTCAATCTGCTCCGAGGTGAA-3’ |
GP α1—Fwd | 5’-CAGGGATATGGATGAACTGAAGAA-3’ |
GP α1—Rev | 5’-GTGTGAGGGAATTAGGACCATCTC-3’ |
GP α3—Fwd | 5’-GGAGTGGGCATCATTTCTGAGG-3’ |
GP α3—Rev | 5′-CGTCGATTTGCTCTGAGGTGAA-3′ |
GP α2- Fwd | 5′-CTGTCCTTGGATGAGCTGGGT-3′ |
GP and mouse α2—Rev | 5′-ACTTGACCCACTCAGGAGTTGTGG-3′ |
UL83 F6 | 5′-CGACGACGACGATGACGAAAAC-3′ |
UL83 B11 | 5′-TCCTCGGTCTCAACGAAGGGTC-3′ |
GP-GAPDH—Fwd | 5′-GGGCAAGGTCATCCCAGAG-3′ |
GP-GAPDH—Rev | 5′-TGGAAGAATGGCTGTCACTGTT-3′ |
Gene | Primer Sequence |
---|---|
HCMV IE1—Fwd | 5′-CTTAATACAAGCCATCCACA-3′ |
HCMV IE1—Rev | 5′-TAGATAAGGTTCATGAGCCT-3′ |
HCMV MIEP-derived IE—Fwd | 5′-TTGACCTCCATAGAAGACAC-3′ |
HCMV MIEP-derived IE—Rev | 5′-AGGACTCCATCGTGTCAAGG-3′ |
Human CXCL-10—Fwd | 5′-TTACTGAAAGCAGTTAGCAAGGAA-3’ |
Human CXCL-10—Rev | 5’-AGCTGATTTGGTGACCATCATTG-3’ |
Human IFN-β—Fwd | 5’-GATTCATCTAGCACTGGCTGG-3’ |
Human IFN-β—Rev | 5’-CTTCAGGTAATGCAGAATCC-3’ |
Human IL-8—Fwd | 5’-TGCAGCTCTGTGTGAAGGTGCAGT-3’ |
Human IL-1β—Fwd | 5’-GCTCGCCAGTGAAATGATGGCTT-3’ |
Human IL-1β—Rev | 5’-CAGAGGTCCAGGTCCTGGAAGG -3’ |
Human IL-8—Rev | 5’-CAGTGTGGTCCACTCTCAATCACTC-3’ |
Human GAPDH—Fwd | 5’-TTGGTATCGTGGAAGGACTC-3’ |
Human GAPDH—Rev | 5’-ACAGTCTTCTGGGTGGCAGT-3’ |
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Mei, H.; Cai, H.; Liu, F.; Venkatadri, R.; Miller, H.E.; Mathison, A.J.; Wang, H.-Y.L.; Silva, S.C.; O’Doherty, G.A.; Arav-Boger, R. Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump. Viruses 2025, 17, 398. https://doi.org/10.3390/v17030398
Mei H, Cai H, Liu F, Venkatadri R, Miller HE, Mathison AJ, Wang H-YL, Silva SC, O’Doherty GA, Arav-Boger R. Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump. Viruses. 2025; 17(3):398. https://doi.org/10.3390/v17030398
Chicago/Turabian StyleMei, Hong, Hongyi Cai, Fengjie Liu, Rajkumar Venkatadri, Halli E. Miller, Angela J. Mathison, Hua-Yu Leo Wang, Simone C. Silva, George A. O’Doherty, and Ravit Arav-Boger. 2025. "Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump" Viruses 17, no. 3: 398. https://doi.org/10.3390/v17030398
APA StyleMei, H., Cai, H., Liu, F., Venkatadri, R., Miller, H. E., Mathison, A. J., Wang, H.-Y. L., Silva, S. C., O’Doherty, G. A., & Arav-Boger, R. (2025). Interspecies Differences in Cytomegalovirus Inhibition by Cardiac Glycosides—A Unique Role of the Alpha3 Isoform of the Na+/K+-ATPase Pump. Viruses, 17(3), 398. https://doi.org/10.3390/v17030398