The PACS-2 protein and trafficking motifs in CCHFV Gn and Gc cytoplasmic domains govern CCHFV assembly

• Published in: Emerging microbes & infections Vol. 13; no. 1; p. 2348508
• Main Authors: Gautam, Anupriya, Lalande, Alexandre, Ritter, Maureen, Freitas, Natalia, Lerolle, Solène, Canus, Lola, Amirache, Fouzia, Lotteau, Vincent, Legros, Vincent, Cosset, François-Loïc, Mathieu, Cyrille, Boson, Bertrand
• Format: Journal Article
• Language: English
• Published: United States Earliest : Springer-Nature ; Latest : Taylor & Francis 01-12-2024; Taylor & Francis; Taylor & Francis Group
• Subjects: Amino Acid Motifs; Animals; assembly; CCHFV; Chlorocebus aethiops; glycoprotein; HEK293 Cells; Hemorrhagic Fever Virus, Crimean-Congo - genetics; Hemorrhagic Fever Virus, Crimean-Congo - physiology; Humans; Life Sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Microbiology and Parasitology; nucleoprotein; Protein Domains; Protein Transport; trafficking; Vero Cells; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Virology; Virus Assembly; assembly; nucleoprotein; glycoprotein; trafficking; CCHFV; CCHFV assembly trafficking glycoprotein nucleoprotein
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2024.2348508

The Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus that causes high mortality in humans. This enveloped virus harbors two surface glycoproteins (GP), Gn and Gc, that are released by processing of a glycoprotein precursor complex whose maturation takes place in the ER and is completed through the secretion pathway. Here, we characterized the trafficking network exploited by CCHFV GPs during viral assembly, envelopment, and/or egress. We identified membrane trafficking motifs in the cytoplasmic domains (CD) of CCHFV GPs and addressed how they impact these late stages of the viral life cycle using infection and biochemical assays, and confocal microscopy in virus-producing cells. We found that several of the identified CD motifs modulate GP transport through the retrograde trafficking network, impacting envelopment and secretion of infectious particles. Finally, we identified PACS-2 as a crucial host factor contributing to CCHFV GPs trafficking required for assembly and release of viral particles.