Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: PLoS Pathogens

Bandnummer: 16

Heftnummer: 9

ISSN: 1553-7366

eISSN: 1553-7374

Open Access Status: Gold

DOI Link: https://doi.org/10.1371/journal.ppat.1008850

Verlag: Public Library of Science

Abstract: 

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borneorthonairovirusthat has become a serious threat to the public health. CCHFV has a single-stranded, tripartite RNA genome composed of L, M, and S segments. Cleavage of the M polyprotein precursor generates the two envelope glycoproteins (GPs) as well as three secreted nonstructural proteins GP38 and GP85 or GP160, representing GP38 only or GP38 linked to a mucin-like protein (MLD), and a double-membrane-spanning protein called NSm. Here, we examined the relevance of each M-segment non-structural proteins in virus assembly, egress and infectivity using a well-established CCHFV virus-like-particle system (tc-VLP). Deletion of MLD protein had no impact on infectivity although it reduced by 60% incorporation of GPs into particles. Additional deletion of GP38 abolished production of infectious tc-VLPs. The loss of infectivity was associated with impaired Gc maturation and exclusion from the Golgi, showing that Gn is not sufficient to target CCHFV GPs to the site of assembly. Consistent with this, efficient complementation was achieved in cells expressing MLD-GP38in transwith increased levels of preGc to Gc conversion, co-targeting to the Golgi, resulting in particle incorporation and restored infectivity. Contrastingly, a MLD-GP38 variant retained in the ER allowed preGc cleavage but failed to rescue miss-localization or infectivity. NSm deletion, conversely, did not affect trafficking of Gc but interfered with Gc processing, particle formation and secretion. NSm expression affected N-glycosylation of different viral proteins most likely due to increased speed of trafficking through the secretory pathway. This highlights a potential role of NSm in overcoming Golgi retention and facilitating CCHFV egress. Thus, deletions of GP38 or NSm demonstrate their important role on CCHFV particle production and infectivity. GP85 is an essential viral factor for preGc cleavage, trafficking and Gc incorporation into particles, whereas NSm protein is involved in CCHFV assembly and virion secretion.

Harvard-Zitierstil: Freitas, N., Enguehard, M., Denolly, S., Levy, C., Neveu, G., Lerolle, S., et al. (2020) The interplays between Crimean-Congo hemorrhagic fever virus (CCHFV) M segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity, PLoS Pathogens, 16(9), Article e1008850. https://doi.org/10.1371/journal.ppat.1008850

APA-Zitierstil: Freitas, N., Enguehard, M., Denolly, S., Levy, C., Neveu, G., Lerolle, S., Devignot, S., Weber, F., Bergeron, E., Legros, V., & Cosset, F. (2020). The interplays between Crimean-Congo hemorrhagic fever virus (CCHFV) M segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity. PLoS Pathogens. 16(9), Article e1008850. https://doi.org/10.1371/journal.ppat.1008850