Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface

Pascal S. Roulin, Mark Lötzerich, Federico Torta, Lukas B. Tanner, Frank J.M. Van Kuppeveld, Markus R. Wenk, Urs F. Greber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

182 Citations (Scopus)

Abstract

Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.

Original languageEnglish
Pages (from-to)677-690
Number of pages14
JournalCell Host and Microbe
Volume16
Issue number5
DOIs
Publication statusPublished - 12 Nov 2014
Externally publishedYes

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