A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation
Mumps virus (MuV) is a neurotropic non-segmented, negative-stranded, enveloped RNA virus in the <i>Paramyxovirus</i> family. The 15.4 kb genome encodes seven genes, including the V/P, which encodes, among other proteins, the V protein. The MuV V protein has been shown to target the cellu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/11/11/1016 |
| _version_ | 1828463639973068800 |
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| author | Tahir Malik Laurie Ngo Trent Bosma Steven Rubin |
| author_facet | Tahir Malik Laurie Ngo Trent Bosma Steven Rubin |
| author_sort | Tahir Malik |
| collection | DOAJ |
| description | Mumps virus (MuV) is a neurotropic non-segmented, negative-stranded, enveloped RNA virus in the <i>Paramyxovirus</i> family. The 15.4 kb genome encodes seven genes, including the V/P, which encodes, among other proteins, the V protein. The MuV V protein has been shown to target the cellular signal transducer and activator of transcription proteins STAT1 and STAT3 for proteasome-mediated degradation. While MuV V protein targeting of STAT1 is generally accepted as a means of limiting innate antiviral responses, the consequence of V protein targeting of STAT3 is less clear. Further, since the MuV V protein targets both STAT1 and STAT3, specifically investigating viral antagonism of STAT3 targeting is challenging. However, a previous study reported that a single amino acid substitution in the MuV V protein (E95D) inhibits targeting of STAT3, but not STAT1. This provided us with a unique opportunity to examine the specific role of STAT 3 in MuV virulence in an in vivo model. Here, using a clone of a wild type MuV strain expressing the E95D mutant V protein, we present data linking inhibition of STAT3 targeting with the accelerated clearance of the virus and reduced neurovirulence in vivo, suggesting its role in promoting antiviral responses. These data suggest a rational approach to virus attenuation that could be exploited for future vaccine development. |
| first_indexed | 2024-12-11T02:57:58Z |
| format | Article |
| id | doaj.art-2eebb3216f29471d89763e7baed53d28 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T02:57:58Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2eebb3216f29471d89763e7baed53d282022-12-22T01:23:07ZengMDPI AGViruses1999-49152019-11-011111101610.3390/v11111016v11111016A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus AttenuationTahir Malik0Laurie Ngo1Trent Bosma2Steven Rubin3DVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USADVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USADVP/Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USAGlaxoSmithKline, 14200 Shady Grove Rd, Rockville, MD 20850, USAMumps virus (MuV) is a neurotropic non-segmented, negative-stranded, enveloped RNA virus in the <i>Paramyxovirus</i> family. The 15.4 kb genome encodes seven genes, including the V/P, which encodes, among other proteins, the V protein. The MuV V protein has been shown to target the cellular signal transducer and activator of transcription proteins STAT1 and STAT3 for proteasome-mediated degradation. While MuV V protein targeting of STAT1 is generally accepted as a means of limiting innate antiviral responses, the consequence of V protein targeting of STAT3 is less clear. Further, since the MuV V protein targets both STAT1 and STAT3, specifically investigating viral antagonism of STAT3 targeting is challenging. However, a previous study reported that a single amino acid substitution in the MuV V protein (E95D) inhibits targeting of STAT3, but not STAT1. This provided us with a unique opportunity to examine the specific role of STAT 3 in MuV virulence in an in vivo model. Here, using a clone of a wild type MuV strain expressing the E95D mutant V protein, we present data linking inhibition of STAT3 targeting with the accelerated clearance of the virus and reduced neurovirulence in vivo, suggesting its role in promoting antiviral responses. These data suggest a rational approach to virus attenuation that could be exploited for future vaccine development.https://www.mdpi.com/1999-4915/11/11/1016mumpsnon-segmentednegative-strandedenvelopedrna virusparamyxovirusstatneurovirulence |
| spellingShingle | Tahir Malik Laurie Ngo Trent Bosma Steven Rubin A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation Viruses mumps non-segmented negative-stranded enveloped rna virus paramyxovirus stat neurovirulence |
| title | A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation |
| title_full | A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation |
| title_fullStr | A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation |
| title_full_unstemmed | A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation |
| title_short | A Single Point Mutation in the Mumps V Protein Alters Targeting of the Cellular STAT Pathways Resulting in Virus Attenuation |
| title_sort | single point mutation in the mumps v protein alters targeting of the cellular stat pathways resulting in virus attenuation |
| topic | mumps non-segmented negative-stranded enveloped rna virus paramyxovirus stat neurovirulence |
| url | https://www.mdpi.com/1999-4915/11/11/1016 |
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