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Host lipids required for Membrane protein matrix formation in new severe acute respiratory syndrome‐related coronavirus (SARS‐CoV‐2), ribonucleocapsid packaging and viral assembly
Author(s) -
Amiar Souad,
Stahelin Robert V.
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r1977
Subject(s) - microbiology and biotechnology , biology , sphingolipid , endoplasmic reticulum , ribonucleoprotein , viral matrix protein , golgi apparatus , viral structural protein , viral envelope , viral protein , vp40 , coronavirus , viral entry , glycoprotein , virus , rna , biochemistry , virology , viral replication , covid-19 , gene , medicine , disease , pathology , infectious disease (medical specialty)
The current model of SARS‐CoV‐2 assembly proposes a multistage process: (i) the viral RNA coated with the nucleoprotein (N) forms the ribonucleoprotein (RNP), (ii) traffics to the endoplasmic reticulum‐Golgi apparatus intermediate compartment (ERGIC)‐derived vesicles to (iii) interact with the membrane (M) assembled along with spike (S) and envelope (E) proteins. Coronaviruses’ M has been described as required for new virus particle assembly. To date, biochemical and structural information on M are unavailable and key host factors required for M lattice formation, trafficking and interaction with the RNP are poorly characterized. The objective of this research project is to progress our understanding of SARS‐CoV‐2 assembly. Our central hypothesis is that M through its interaction with host lipids coordinates viral protein interactions and RNP packaging as key processes for SARS‐CoV‐2 assembly and spread . The role of lipids as molecules regulating the viral life cycle is poorly investigated. Our current data demonstrates a clear binding of cell expressed M to a Golgi resident sphingolipid. Furthermore, mutations at the sphingolipid binding motif resulted in deficient pull down of M protein by sphingolipid coated beads. In cells, the M sphingolipid‐binding mutant failed to retain S protein at viral assembly membranes resulting in a reduced entry capacity of newly formed virus‐like particles. Our current study is providing a first insight on the direct role of host lipids during SARS‐CoV‐2 assembly, orchestrated by the M protein.