How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics
Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mech...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/6/1303 |
| _version_ | 1827735370765172736 |
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| author | Lubna Pinky Joseph R. DeAguero Christopher H. Remien Amber M. Smith |
| author_facet | Lubna Pinky Joseph R. DeAguero Christopher H. Remien Amber M. Smith |
| author_sort | Lubna Pinky |
| collection | DOAJ |
| description | Respiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral–viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral–viral coinfections in this way provides new insights about how viral–viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation. |
| first_indexed | 2024-03-11T01:50:05Z |
| format | Article |
| id | doaj.art-6eee5c0f17d0452d808f0a632ce9d61d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T01:50:05Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-6eee5c0f17d0452d808f0a632ce9d61d2023-11-18T13:01:52ZengMDPI AGViruses1999-49152023-05-01156130310.3390/v15061303How Interactions during Viral–Viral Coinfection Can Shape Infection KineticsLubna Pinky0Joseph R. DeAguero1Christopher H. Remien2Amber M. Smith3Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USABioinformatics and Computational Biology Program, University of Idaho, Moscow, ID 83844, USADepartment of Mathematics and Statistical Science, University of Idaho, Moscow, ID 83844, USADepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USARespiratory viral infections are a leading global cause of disease with multiple viruses detected in 20–30% of cases, and several viruses simultaneously circulating. Some infections with unique viral copathogens result in reduced pathogenicity, while other viral pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral–viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV), followed by influenza A virus (IAV) after 3 days. The results suggest that IAV reduced the rate of RSV production, while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios that had not been examined experimentally, including a different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight-loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis shows that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to the slower clearance of IAV-infected cells by the other viruses. The improved outcome when IAV followed RV, on the other hand, could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral–viral coinfections in this way provides new insights about how viral–viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.https://www.mdpi.com/1999-4915/15/6/1303viral coinfectioninfluenzaRSVrhinovirusSARS-CoV-2viral dynamics |
| spellingShingle | Lubna Pinky Joseph R. DeAguero Christopher H. Remien Amber M. Smith How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics Viruses viral coinfection influenza RSV rhinovirus SARS-CoV-2 viral dynamics |
| title | How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics |
| title_full | How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics |
| title_fullStr | How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics |
| title_full_unstemmed | How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics |
| title_short | How Interactions during Viral–Viral Coinfection Can Shape Infection Kinetics |
| title_sort | how interactions during viral viral coinfection can shape infection kinetics |
| topic | viral coinfection influenza RSV rhinovirus SARS-CoV-2 viral dynamics |
| url | https://www.mdpi.com/1999-4915/15/6/1303 |
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