Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics
<i>Rotavirus A</i> (RVA) genome segments can reassort upon co-infection of target cells with two different RVA strains. However, not all reassortants are viable, which limits the ability to generate customized viruses for basic and applied research. To gain insight into the factors that...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5670 |
| _version_ | 1797611215479898112 |
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| author | Roman Valusenko-Mehrkens Ashish K. Gadicherla Reimar Johne Alexander Falkenhagen |
| author_facet | Roman Valusenko-Mehrkens Ashish K. Gadicherla Reimar Johne Alexander Falkenhagen |
| author_sort | Roman Valusenko-Mehrkens |
| collection | DOAJ |
| description | <i>Rotavirus A</i> (RVA) genome segments can reassort upon co-infection of target cells with two different RVA strains. However, not all reassortants are viable, which limits the ability to generate customized viruses for basic and applied research. To gain insight into the factors that restrict reassortment, we utilized reverse genetics and tested the generation of simian RVA strain SA11 reassortants carrying the human RVA strain Wa capsid proteins VP4, VP7, and VP6 in all possible combinations. VP7-Wa, VP6-Wa, and VP7/VP6-Wa reassortants were effectively rescued, but the VP4-Wa, VP4/VP7-Wa, and VP4/VP6-Wa reassortants were not viable, suggesting a limiting effect of VP4-Wa. However, a VP4/VP7/VP6-Wa triple-reassortant was successfully generated, indicating that the presence of homologous VP7 and VP6 enabled the incorporation of VP4-Wa into the SA11 backbone. The replication kinetics of the triple-reassortant and its parent strain Wa were comparable, while the replication of all other rescued reassortants was similar to SA11. Analysis of the predicted structural protein interfaces identified amino acid residues, which might influence protein interactions. Restoring the natural VP4/VP7/VP6 interactions may therefore improve the rescue of RVA reassortants by reverse genetics, which could be useful for the development of next generation RVA vaccines. |
| first_indexed | 2024-03-11T06:24:41Z |
| format | Article |
| id | doaj.art-0ba5c55068da446ebd65feabd89e4ddf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:24:41Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0ba5c55068da446ebd65feabd89e4ddf2023-11-17T11:37:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246567010.3390/ijms24065670Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse GeneticsRoman Valusenko-Mehrkens0Ashish K. Gadicherla1Reimar Johne2Alexander Falkenhagen3Department of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, GermanyDepartment of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, GermanyDepartment of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, GermanyDepartment of Biological Safety, German Federal Institute for Risk Assessment, 10589 Berlin, Germany<i>Rotavirus A</i> (RVA) genome segments can reassort upon co-infection of target cells with two different RVA strains. However, not all reassortants are viable, which limits the ability to generate customized viruses for basic and applied research. To gain insight into the factors that restrict reassortment, we utilized reverse genetics and tested the generation of simian RVA strain SA11 reassortants carrying the human RVA strain Wa capsid proteins VP4, VP7, and VP6 in all possible combinations. VP7-Wa, VP6-Wa, and VP7/VP6-Wa reassortants were effectively rescued, but the VP4-Wa, VP4/VP7-Wa, and VP4/VP6-Wa reassortants were not viable, suggesting a limiting effect of VP4-Wa. However, a VP4/VP7/VP6-Wa triple-reassortant was successfully generated, indicating that the presence of homologous VP7 and VP6 enabled the incorporation of VP4-Wa into the SA11 backbone. The replication kinetics of the triple-reassortant and its parent strain Wa were comparable, while the replication of all other rescued reassortants was similar to SA11. Analysis of the predicted structural protein interfaces identified amino acid residues, which might influence protein interactions. Restoring the natural VP4/VP7/VP6 interactions may therefore improve the rescue of RVA reassortants by reverse genetics, which could be useful for the development of next generation RVA vaccines.https://www.mdpi.com/1422-0067/24/6/5670rotavirusreassortmentVP4VP7VP6reverse genetics system |
| spellingShingle | Roman Valusenko-Mehrkens Ashish K. Gadicherla Reimar Johne Alexander Falkenhagen Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics International Journal of Molecular Sciences rotavirus reassortment VP4 VP7 VP6 reverse genetics system |
| title | Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics |
| title_full | Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics |
| title_fullStr | Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics |
| title_full_unstemmed | Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics |
| title_short | Strain-Specific Interactions between the Viral Capsid Proteins VP4, VP7 and VP6 Influence Rescue of Rotavirus Reassortants by Reverse Genetics |
| title_sort | strain specific interactions between the viral capsid proteins vp4 vp7 and vp6 influence rescue of rotavirus reassortants by reverse genetics |
| topic | rotavirus reassortment VP4 VP7 VP6 reverse genetics system |
| url | https://www.mdpi.com/1422-0067/24/6/5670 |
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