<em>Orthoparamyxovirinae</em> C Proteins Have a Common Origin and a Common Structural Organization - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2023

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

Résumé

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.

Dates et versions

hal-03959596 , version 1 (27-01-2023)

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Ada Roy, Emeric Chan Mine, Lorenzo Gaifas, Cedric Leyrat, Valentina Volchkova, et al.. Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization. 2023. ⟨hal-03959596⟩
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