Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus

• DOI: 10.1371/journal.ppat.1011052
• Publication Date: 2023-07-28T17:35:52Z
• Authors: Minh-Tu Pham; Ji-Young Lee; Christian Ritter; Roman Thielemann; Janis Meyer; Uta Haselmann; Charlotta Funaya; Vibor Laketa; Karl Rohr; Ralf Bartenschlager
• Keywords: Apolipoprotein E; NS5A

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result several metabolic disorders genotypes have been associated with multiple diseases. is synthesized at the endoplasmic reticulum transported to Golgi apparatus for LP assembly; however, ApoE-LPs pathway from there membrane largely unknown. Here, we established an integrative imaging approach based on a fully functional fluorescently tagged ApoE. We found that newly accumulate CD63-positive endosomes hepatocytes. In addition, observed co-egress intraluminal vesicles (ILVs), which are precursors extracellular (EVs), along late endosomal trafficking route microtubule-dependent manner. A fraction EVs appears be co-transmitted cell cell. Given important role viral infections, employed as well-studied model hepatitis C virus (HCV) replicase component nonstructural protein 5A (NS5A) enriched ApoE-containing ILVs. Interaction between NS5A required efficient release ILVs containing HCV RNA. These egress pathway. Taken together, our data argue transmission hepatic ApoE-LPs, hijacked by HCV. more general EV-mediated cell-to-cell communication, these insights provide new starting points research into pathophysiology ApoE-related infection-related disorders.