Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model
Abstract
:1. Introduction
2. Material and Methods
2.1. Cells and Viruses
2.2. Plasmid-Based Reverse Genetics
2.3. Replication Kinetics
2.4. Animal Ethics Statement
2.5. Ferret Screening
2.6. Transmission Studies
2.7. Serology Assays
2.8. Tissue Sample Collection
2.9. In Vitro HA pH Inactivation Assay
3. Results
3.1. Viruses with Cell-Culture-Adaptive HA Mutations Replicated Better in MDCK Cells
3.2. The pH of Inactivation rPerth Mutant Was Higher Than That of WT
3.3. Replication of the rPerth Mutant in Ferrets Was Similar to WT
3.4. H3N2 Mutant Virus with a Higher pH of Fusion Had Reduced Airborne Transmission to Naïve Ferrets
3.5. NA-Segment Noncoding Regions Influence the Virus pH of Fusion
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Virus | Exposure Time | Status | Transmission Efficiency | Temperature Increase * | Weight loss* | H3N2 Microneutralization Titers ^ | HAI Titers ^^ |
---|---|---|---|---|---|---|---|
rPerth WT | 14 days | INF | 0/3 | 0/3 | 2560, 250, 2560 | 2560, 250, 2560 | |
Naïve | 3/3 | 1/3 | 0/3 | 1280, 2560, 1280 | 1280, 2560, 1280 | ||
rPerth mutant | 14 days | INF | 1/3 | 0/3 | 2260, 1010, 2260 | 1280, 1280, 690 | |
Naïve | 1/3 | 1/3 | 0/3 | <20, <20, 1010 | <10, <10, 2560 |
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Le Sage, V.; Kormuth, K.A.; Nturibi, E.; Lee, J.M.; Frizzell, S.A.; Myerburg, M.M.; Bloom, J.D.; Lakdawala, S.S. Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model. Viruses 2021, 13, 719. https://doi.org/10.3390/v13050719
Le Sage V, Kormuth KA, Nturibi E, Lee JM, Frizzell SA, Myerburg MM, Bloom JD, Lakdawala SS. Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model. Viruses. 2021; 13(5):719. https://doi.org/10.3390/v13050719
Chicago/Turabian StyleLe Sage, Valerie, Karen A. Kormuth, Eric Nturibi, Juhye M. Lee, Sheila A. Frizzell, Michael M. Myerburg, Jesse D. Bloom, and Seema S. Lakdawala. 2021. "Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model" Viruses 13, no. 5: 719. https://doi.org/10.3390/v13050719
APA StyleLe Sage, V., Kormuth, K. A., Nturibi, E., Lee, J. M., Frizzell, S. A., Myerburg, M. M., Bloom, J. D., & Lakdawala, S. S. (2021). Cell-Culture Adaptation of H3N2 Influenza Virus Impacts Acid Stability and Reduces Airborne Transmission in Ferret Model. Viruses, 13(5), 719. https://doi.org/10.3390/v13050719