Year: 2022
Type: article
Abstract: Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles, MCSs remain largely unexplored during infections. Here, we design a targeted proteomics platform for measuring MCS proteins at all organelles simultaneously and define functional virus-driven MCS alterations by the ancient beta-herpesvirus human cytomegalovirus (HCMV). Integration with super-resolution microscopy and comparisons to herpes simplex virus (HSV-1), Influenza A, and beta-coronavirus HCoV-OC43 infections reveals time-sensitive contact regulation that allows switching anti- to pro-viral organelle functions. We uncover a stabilized mitochondria-ER encapsulation structure (MENC). As HCMV infection progresses, MENCs become the predominant mitochondria-ER contact phenotype and sequentially recruit the tethering partners VAP-B and PTPIP51, supporting virus production. However, premature ER-mitochondria tethering activates STING and interferon response, priming cells against infection. At peroxisomes, ACBD5-mediated ER contacts balance peroxisome proliferation versus membrane expansion, with ACBD5 impacting the titers of each virus tested.
Source: Nature Communications
Institutions: Princeton University, University of Alabama at Birmingham
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: Predoctoral Training in Genetics and Molecular Biology, G2568872698, G2802527627, G2933921233, G329246016, Training Program in Cell, Molecular, and Developmental Biology, Dynamic organelle membrane contacts as key regulators of virus replication, G5314748276, Mechanisms mediating immune response upon sensing of nuclear viral DNA, G6366735736, G8086714402, Dynamic virus-driven remodeling of ER-mitochondria contacts
OpenAlex ID: W4291004576