Proteomics

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Quantification of organelle membrane contact site protein abundances during infection with human viruses


ABSTRACT: Viruses rely on organelles to invade, replicate, and spread between host cells. Likewise, organelles underlie the host's ability to sense and respond to pathogen invasion. To subvert cellular functions and turn them to the benefit of virus production and spread, viruses remodel organelle structure and function during infection. We predicted that membrane contact sites (MCSs) underlie virus-driven organelle remodeling events. MCSs use protein interactions to bridge organelle membranes for the direct transfer of biomolecules, coordinating fundamental organelle dynamics. The extent of contact and potential functions of MCSs are dictated by the abundance of MCS-specific proteins at organelle interfaces. Here, we design a parallel reaction monitoring (PRM) targeted MS assay to quantify MCS protein abundances across time and space. Our assay encompasses nearly all MCS functions and all major cellular organelles (ER, mitochondria, peroxisome, endosomes, lysosomes, autophagosomes, lipid droplets, plasma membrane, Golgi), with 2-5 signature peptides per protein and internal controls. Utilizing MCS-PRM, we uncover temporal- and organelle-specific regulation of MCSs during the infectious cycles of critical human viruses: the beta-herpesvirus human cytomegalovirus (HCMV, also known as HHV-5), herpes simplex virus type 1 (HSV-1), the orthomyxovirus influenza A (Infl. A PR8), and the beta-coronavirus HCoV-OC43.

ORGANISM(S): Homo Sapiens Human Coronavirus Oc43 Influenza A Virus (a/puerto Rico/8/1934(h1n1)) Human Betaherpesvirus 5 Human Alphaherpesvirus 1

SUBMITTER: Katelyn Cook  

PROVIDER: PXD023761 | panorama | Fri Jul 08 00:00:00 BST 2022

REPOSITORIES: PanoramaPublic

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