Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization
Abstract
The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a minireplicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.
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BibTeX
@article{roy2026orthoparamyxovirinae,
title = {{Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization}},
author = {Ada Roy and Emeric Chan Mine and Lorenzo Gaifas and Cédric Leyrat and Valentina A Volchkova and Florence Baudin and Luis Martinez-Gil and Viktor E Volchkov and David G Karlin and Jean-Marie Bourhis and Marc Jamin},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom13030455},
url = {https://hal.science/hal-05796746v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization
AU - Ada Roy
AU - Emeric Chan Mine
AU - Lorenzo Gaifas
AU - Cédric Leyrat
AU - Valentina A Volchkova
AU - Florence Baudin
AU - Luis Martinez-Gil
AU - Viktor E Volchkov
AU - David G Karlin
AU - Jean-Marie Bourhis
AU - Marc Jamin
PY - 2026
DA - 2026/10/13
JO - Biomolecules
DO - 10.3390/biom13030455
UR - https://hal.science/hal-05796746v1
AB - The protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 Å and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a minireplicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to.
SN - 2218-273X
ER -