Restructured membrane contacts rewire organelles for human cytomegalovirus infection.

TitleRestructured membrane contacts rewire organelles for human cytomegalovirus infection.
Publication TypeJournal Article
Year of Publication2022
AuthorsCook, KC, Tsopurashvili, E, Needham, JM, Thompson, SR, Cristea, IM
JournalNat Commun
Volume13
Issue1
Pagination4720
Date Published2022 Aug 11
ISSN2041-1723
KeywordsCytomegalovirus, Cytomegalovirus Infections, Herpes Simplex, Herpesviridae Infections, Humans, Organelles, Peroxisomes, Viruses
Abstract

<p>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.</p>

DOI10.1038/s41467-022-32488-6
Alternate JournalNat Commun
PubMed ID35953480
PubMed Central IDPMC9366835
Grant ListF31 AI147637 / AI / NIAID NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States