Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization

Ada Roy
,
Emeric Chan Mine
,
Lorenzo Gaifas
,
Cédric Leyrat
ORCID logo ,
Valentina Volchkova
,
Florence Baudin
,
Luis Martinez-Gil
,
Viktor Volchkov
,
David G. Karlin
* ORCID logo ,
Jean-Marie Bourhis
,
Marc Jamin
* ORCID logo
Version 1 : Received: 11 January 2023 / Approved: 12 January 2023 / Online: 12 January 2023 (08:50:26 CET)

A peer-reviewed article of this Preprint also exists.

Roy, A.; Chan Mine, E.; Gaifas, L.; Leyrat, C.; Volchkova, V.A.; Baudin, F.; Martinez-Gil, L.; Volchkov, V.E.; Karlin, D.G.; Bourhis, J.-M.; Jamin, M. Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization. Biomolecules 2023, 13, 455. Roy, A.; Chan Mine, E.; Gaifas, L.; Leyrat, C.; Volchkova, V.A.; Baudin, F.; Martinez-Gil, L.; Volchkov, V.E.; Karlin, D.G.; Bourhis, J.-M.; Jamin, M. Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization. Biomolecules 2023, 13, 455.

Abstract

The protein C is a small viral protein encoded in an overlapping frame of the P gene in the sub-family 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 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 NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins former 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 representative of these two clusters, our discovery that they have a similar structure indi-cates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strik-ingly, 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.

Keywords

Paramyxoviridae; virulence factor; overlapping genes; protein structure; viral evolutio

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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