Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures
Measles virus (MV) can cause severe acute diseases as well as long-lasting clinical deteriorations due to viral-induced immunosuppression and neuronal manifestation. How the virus enters the brain and manages to persist in neuronal tissue is not fully understood. Various mutations in the viral genes...
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MDPI AG
2021-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/4/605 |
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| author | Johannes Busch Soroth Chey Michael Sieg Thomas W. Vahlenkamp Uwe G. Liebert |
| author_facet | Johannes Busch Soroth Chey Michael Sieg Thomas W. Vahlenkamp Uwe G. Liebert |
| author_sort | Johannes Busch |
| collection | DOAJ |
| description | Measles virus (MV) can cause severe acute diseases as well as long-lasting clinical deteriorations due to viral-induced immunosuppression and neuronal manifestation. How the virus enters the brain and manages to persist in neuronal tissue is not fully understood. Various mutations in the viral genes were found in MV strains isolated from patient brains. In this study, reverse genetics was used to introduce mutations in the fusion, matrix and polymerase genes of MV. The generated virus clones were characterized in cell culture and used to infect rat brain slice cultures. A mutation in the carboxy-terminal domain of the matrix protein (R293Q) promoted the production of progeny virions. This effect was observed in Vero cells irrespective of the expression of the signaling lymphocyte activation molecule (SLAM). Furthermore, a mutation in the fusion protein (I225M) induced syncytia formation on Vero cells in the absence of SLAM and promoted viral spread throughout the rat brain slices. In this study, a solid ex vivo model was established to elucidate the MV mutations contributing to neural manifestation. |
| first_indexed | 2024-03-10T12:40:40Z |
| format | Article |
| id | doaj.art-7038093ccaa54d8d825a53d1131a8cbe |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T12:40:40Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7038093ccaa54d8d825a53d1131a8cbe2023-11-21T13:53:12ZengMDPI AGViruses1999-49152021-04-0113460510.3390/v13040605Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice CulturesJohannes Busch0Soroth Chey1Michael Sieg2Thomas W. Vahlenkamp3Uwe G. Liebert4Institute of Virology, University Hospital Leipzig, Johannisallee 30, 04103 Leipzig, GermanyInstitute of Virology, University Hospital Leipzig, Johannisallee 30, 04103 Leipzig, GermanyFaculty of Veterinary Medicine, Institute of Virology, Leipzig University, An den Tierkliniken 29, 04103 Leipzig, GermanyFaculty of Veterinary Medicine, Institute of Virology, Leipzig University, An den Tierkliniken 29, 04103 Leipzig, GermanyInstitute of Virology, University Hospital Leipzig, Johannisallee 30, 04103 Leipzig, GermanyMeasles virus (MV) can cause severe acute diseases as well as long-lasting clinical deteriorations due to viral-induced immunosuppression and neuronal manifestation. How the virus enters the brain and manages to persist in neuronal tissue is not fully understood. Various mutations in the viral genes were found in MV strains isolated from patient brains. In this study, reverse genetics was used to introduce mutations in the fusion, matrix and polymerase genes of MV. The generated virus clones were characterized in cell culture and used to infect rat brain slice cultures. A mutation in the carboxy-terminal domain of the matrix protein (R293Q) promoted the production of progeny virions. This effect was observed in Vero cells irrespective of the expression of the signaling lymphocyte activation molecule (SLAM). Furthermore, a mutation in the fusion protein (I225M) induced syncytia formation on Vero cells in the absence of SLAM and promoted viral spread throughout the rat brain slices. In this study, a solid ex vivo model was established to elucidate the MV mutations contributing to neural manifestation.https://www.mdpi.com/1999-4915/13/4/605measles virusreverse geneticsmutagenesisbrain slice cultureneurotropism |
| spellingShingle | Johannes Busch Soroth Chey Michael Sieg Thomas W. Vahlenkamp Uwe G. Liebert Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures Viruses measles virus reverse genetics mutagenesis brain slice culture neurotropism |
| title | Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures |
| title_full | Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures |
| title_fullStr | Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures |
| title_full_unstemmed | Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures |
| title_short | Mutated Measles Virus Matrix and Fusion Protein Influence Viral Titer In Vitro and Neuro-Invasion in Lewis Rat Brain Slice Cultures |
| title_sort | mutated measles virus matrix and fusion protein influence viral titer in vitro and neuro invasion in lewis rat brain slice cultures |
| topic | measles virus reverse genetics mutagenesis brain slice culture neurotropism |
| url | https://www.mdpi.com/1999-4915/13/4/605 |
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