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Restructured membrane contacts rewire organelles for human cytomegalovirus infection

Author

Listed:
  • Katelyn C. Cook

    (Princeton University)

  • Elene Tsopurashvili

    (Princeton University)

  • Jason M. Needham

    (University of Alabama Birmingham)

  • Sunnie R. Thompson

    (University of Alabama Birmingham)

  • Ileana M. Cristea

    (Princeton University)

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.

Suggested Citation

  • Katelyn C. Cook & Elene Tsopurashvili & Jason M. Needham & Sunnie R. Thompson & Ileana M. Cristea, 2022. "Restructured membrane contacts rewire organelles for human cytomegalovirus infection," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32488-6
    DOI: 10.1038/s41467-022-32488-6
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    1. William A. Hofstadter & Katelyn C. Cook & Elene Tsopurashvili & Robert Gebauer & Vojtěch Pražák & Emily A. Machala & Ji Woo Park & Kay Grünewald & Emmanuelle R. J. Quemin & Ileana M. Cristea, 2024. "Infection-induced peripheral mitochondria fission drives ER encapsulations and inter-mitochondria contacts that rescue bioenergetics," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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