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

## TL;DR

This study explores how the Crimean-Congo hemorrhagic fever virus assembles and releases by analyzing protein trafficking and a key host factor, PACS-2.

## Contribution

The study identifies specific trafficking motifs and the role of PACS-2 in CCHFV glycoprotein transport and viral assembly.

## Key findings

- Cytoplasmic domain motifs in CCHFV glycoproteins influence retrograde trafficking and viral envelopment.
- PACS-2 is a critical host factor for CCHFV glycoprotein trafficking and viral particle release.
- Infection and imaging assays reveal how GP transport affects the late stages of the viral life cycle.

## Abstract

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.