A novel accessory gene product of tick-borne Dhori-Orthomyxovirus, encoded by overlooked spliced transcripts of RNA segment 6
Dhori virus (DHOV) (Orthomyxoviridae, genus: Thogotovirus) is a tick-borne virus with a segmented, negative-sense RNA genome. Thogotoviruses can be divided into two clades, Thogoto-like and Dhori-like viruses, which differ in their coding strategy of the segment 6 encoded matrix protein (M): Thogoto...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
Oct 2025
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| In: |
Journal of virology
Year: 2025, Jahrgang: 99, Heft: 10, Pages: 1-30 |
| ISSN: | 1098-5514 |
| DOI: | 10.1128/jvi.00600-25 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1128/jvi.00600-25
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| Verfasserangaben: | E. Bendl, G. Lampo, P. Chlanda, E. Schnettler, G. Kochs, J. Dengjel, L. Graf |
MARC
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| 100 | 1 | |a Bendl, Elias |e VerfasserIn |0 (DE-588)1376172550 |0 (DE-627)1935624369 |4 aut | |
| 245 | 1 | 2 | |a A novel accessory gene product of tick-borne Dhori-Orthomyxovirus, encoded by overlooked spliced transcripts of RNA segment 6 |c E. Bendl, G. Lampo, P. Chlanda, E. Schnettler, G. Kochs, J. Dengjel, L. Graf |
| 264 | 1 | |c Oct 2025 | |
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| 500 | |a Veröffentlicht: 15 September 2025 | ||
| 500 | |a Gesehen am 30.01.2026 | ||
| 520 | |a Dhori virus (DHOV) (Orthomyxoviridae, genus: Thogotovirus) is a tick-borne virus with a segmented, negative-sense RNA genome. Thogotoviruses can be divided into two clades, Thogoto-like and Dhori-like viruses, which differ in their coding strategy of the segment 6 encoded matrix protein (M): Thogoto viruses translate M from spliced transcripts and a long M (ML) from unspliced transcripts. Dhori-like viruses encode their M using unspliced transcripts, whereas no splicing or additional coding capacity has been described, yet. Here, we identified spliced transcripts of segment 6 in DHOV-infected cells by RT-PCR and sequencing. The gene product M2-248 codes for a truncated, 186 amino acids-long N-terminal moiety of M fused to 62 C-terminal amino acids from a -1 shifted reading frame. The splicing sites and the amino acid sequences of the C-terminal M2 part are conserved in Dhori-like viruses. Expression of M2-248 was confirmed in infected cells by mass spectrometry and western blot analysis and was detected in purified virions. Recombinant DHOV(Delta M2) lacking M2-248 showed reduced virulence compared with recombinant wild-type in mice but no attenuation in cell culture and no effect on virion assembly and morphology. An interferon antagonistic function of M2-248, similar to THOV ML, was excluded. Thus, our data suggest that DHOV segment 6 splicing and expression of M2-248 protein affect virulence in mammals by a mechanism distinct from THOV-ML. It remains to be analyzed how M2-248 might affect viral host switch and replication in ticks.IMPORTANCEDhori and Thogoto viruses are tick-transmitted orthomyxoviruses comprising two clades differing in the coding strategy of their matrix protein. The recent detection of Dhori-like Bourbon virus (BRBV) highlighted their zoonotic potential. M of Dhori-like viruses is translated from a collinear transcript of the smallest of the six genomic ssRNA segments. Thogoto-like viruses express M from spliced transcripts, and unspliced transcripts encode an extended ML protein. No analogous splicing event or additional gene product has been characterized for Dhori-like viruses, yet. Here, we describe the hitherto overlooked splicing of segment 6 transcripts of Dhori virus. The 5'-part of the processed transcript is collinear with the M-ORF, whereas splicing shifts it into a -1 frame. The predicted product M2-248 was detected in infected cells. Recombinant Dhori virus lacking M2 was attenuated in vivo, whereas replication in mammalian cells was not impaired, suggesting a modulatory function of M2 in in vivo-specific, cellular immunity-related processes. | ||
| 650 | 4 | |a ACTIVATION | |
| 650 | 4 | |a AGENT | |
| 650 | 4 | |a arbovirus | |
| 650 | 4 | |a Bourbon virus | |
| 650 | 4 | |a CELL-LINES | |
| 650 | 4 | |a Dhori virus | |
| 650 | 4 | |a DISEASE | |
| 650 | 4 | |a HUMAN MXA PROTEIN | |
| 650 | 4 | |a INFECTION | |
| 650 | 4 | |a matrix protein | |
| 650 | 4 | |a new accessory viral gene product | |
| 650 | 4 | |a NUCLEOTIDE-SEQUENCE | |
| 650 | 4 | |a orthomyxoviruses | |
| 650 | 4 | |a SYSTEM | |
| 650 | 4 | |a THOGOTO-VIRUS | |
| 650 | 4 | |a thogotoviruses | |
| 650 | 4 | |a tick-borne | |
| 650 | 4 | |a VIRUS MATRIX PROTEIN | |
| 700 | 1 | |a Lampo, G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Chlanda, Petr |e VerfasserIn |0 (DE-588)141254823 |0 (DE-627)626165261 |0 (DE-576)323011152 |4 aut | |
| 700 | 1 | |a Schnettler, E. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kochs, G. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dengjel, J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Graf, L. |e VerfasserIn |4 aut | |
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| 773 | 1 | 8 | |g volume:99 |g year:2025 |g number:10 |g month:10 |g pages:1-30 |g extent:30 |a A novel accessory gene product of tick-borne Dhori-Orthomyxovirus, encoded by overlooked spliced transcripts of RNA segment 6 |
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