An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles
The major envelope protein E of flaviviruses contains an ectodomain that is connected to the transmembrane domain by the so-called “stem” region. In mature flavivirus particles, the stem is composed of two or three mostly amphipathic α-helices and a conserved sequence element (CS) with an undefined...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/9/1727 |
| _version_ | 1797516988893888512 |
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| author | Iris Medits Franz X. Heinz Karin Stiasny |
| author_facet | Iris Medits Franz X. Heinz Karin Stiasny |
| author_sort | Iris Medits |
| collection | DOAJ |
| description | The major envelope protein E of flaviviruses contains an ectodomain that is connected to the transmembrane domain by the so-called “stem” region. In mature flavivirus particles, the stem is composed of two or three mostly amphipathic α-helices and a conserved sequence element (CS) with an undefined role in the viral life cycle. A tryptophan is the only residue within this region which is not only conserved in all vector-borne flaviviruses, but also in the group with no known vector. We investigated the importance of this residue in different stages of the viral life cycle by a mutagenesis-based approach using tick-borne encephalitis virus (TBEV). Replacing W421 by alanine or histidine strongly reduced the release of infectious virions and their thermostability, whereas fusion-related entry functions and virus maturation were still intact. Serial passaging of the mutants led to the emergence of a same-site compensatory mutation to leucine that largely restored these properties of the wildtype. The conserved tryptophan in CS (or another big hydrophobic amino acid at the same position) is thus essential for the assembly and infectivity of flaviviruses by being part of a network required for conferring stability to infectious particles. |
| first_indexed | 2024-03-10T07:08:35Z |
| format | Article |
| id | doaj.art-548d8ac9abe74571b3a62f3994ed03fb |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T07:08:35Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-548d8ac9abe74571b3a62f3994ed03fb2023-11-22T15:37:05ZengMDPI AGViruses1999-49152021-08-01139172710.3390/v13091727An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable ParticlesIris Medits0Franz X. Heinz1Karin Stiasny2Center for Virology, Medical University of Vienna, 1090 Vienna, AustriaCenter for Virology, Medical University of Vienna, 1090 Vienna, AustriaCenter for Virology, Medical University of Vienna, 1090 Vienna, AustriaThe major envelope protein E of flaviviruses contains an ectodomain that is connected to the transmembrane domain by the so-called “stem” region. In mature flavivirus particles, the stem is composed of two or three mostly amphipathic α-helices and a conserved sequence element (CS) with an undefined role in the viral life cycle. A tryptophan is the only residue within this region which is not only conserved in all vector-borne flaviviruses, but also in the group with no known vector. We investigated the importance of this residue in different stages of the viral life cycle by a mutagenesis-based approach using tick-borne encephalitis virus (TBEV). Replacing W421 by alanine or histidine strongly reduced the release of infectious virions and their thermostability, whereas fusion-related entry functions and virus maturation were still intact. Serial passaging of the mutants led to the emergence of a same-site compensatory mutation to leucine that largely restored these properties of the wildtype. The conserved tryptophan in CS (or another big hydrophobic amino acid at the same position) is thus essential for the assembly and infectivity of flaviviruses by being part of a network required for conferring stability to infectious particles.https://www.mdpi.com/1999-4915/13/9/1727flavivirusesenvelope protein Estem regionflavivirus assemblytick-borne encephalitis virus |
| spellingShingle | Iris Medits Franz X. Heinz Karin Stiasny An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles Viruses flaviviruses envelope protein E stem region flavivirus assembly tick-borne encephalitis virus |
| title | An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles |
| title_full | An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles |
| title_fullStr | An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles |
| title_full_unstemmed | An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles |
| title_short | An Absolutely Conserved Tryptophan in the Stem of the Envelope Protein E of Flaviviruses Is Essential for the Formation of Stable Particles |
| title_sort | absolutely conserved tryptophan in the stem of the envelope protein e of flaviviruses is essential for the formation of stable particles |
| topic | flaviviruses envelope protein E stem region flavivirus assembly tick-borne encephalitis virus |
| url | https://www.mdpi.com/1999-4915/13/9/1727 |
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