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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. Francesca Vallese & Cristina Catoni & Domenico Cieri & Lucia Barazzuol & Omar Ramirez & Valentina Calore & Massimo Bonora & Flavia Giamogante & Paolo Pinton & Marisa Brini & Tito Calì, 2020. "An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Takuma Yoshizumi & Takeshi Ichinohe & Osamu Sasaki & Hidenori Otera & Shun-ichiro Kawabata & Katsuyoshi Mihara & Takumi Koshiba, 2014. "Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    3. Jason E. Lee & Laura M. Westrate & Haoxi Wu & Cynthia Page & Gia K. Voeltz, 2016. "Multiple dynamin family members collaborate to drive mitochondrial division," Nature, Nature, vol. 540(7631), pages 139-143, December.
    4. Steffen Klein & Mirko Cortese & Sophie L. Winter & Moritz Wachsmuth-Melm & Christopher J. Neufeldt & Berati Cerikan & Megan L. Stanifer & Steeve Boulant & Ralf Bartenschlager & Petr Chlanda, 2020. "SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    5. Simone M. Haag & Muhammet F. Gulen & Luc Reymond & Antoine Gibelin & Laurence Abrami & Alexiane Decout & Michael Heymann & F. Gisou van der Goot & Gerardo Turcatti & Rayk Behrendt & Andrea Ablasser, 2018. "Targeting STING with covalent small-molecule inhibitors," Nature, Nature, vol. 559(7713), pages 269-273, July.
    6. Hyun jin Choi & Areum Park & Sujin Kang & Eunhye Lee & Taeyun A. Lee & Eun A. Ra & Jiseon Lee & Sungwook Lee & Boyoun Park, 2018. "Human cytomegalovirus-encoded US9 targets MAVS and STING signaling to evade type I interferon immune responses," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    7. L. A. Murray & X. Sheng & I. M. Cristea, 2018. "Orchestration of protein acetylation as a toggle for cellular defense and virus replication," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    8. Alex M. Valm & Sarah Cohen & Wesley R. Legant & Justin Melunis & Uri Hershberg & Eric Wait & Andrew R. Cohen & Michael W. Davidson & Eric Betzig & Jennifer Lippincott-Schwartz, 2017. "Applying systems-level spectral imaging and analysis to reveal the organelle interactome," Nature, Nature, vol. 546(7656), pages 162-167, June.
    9. Hiroki Ishikawa & Zhe Ma & Glen N. Barber, 2009. "STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity," Nature, Nature, vol. 461(7265), pages 788-792, October.
    10. Soojin Kim & Yvette C. Wong & Fanding Gao & Dimitri Krainc, 2021. "Dysregulation of mitochondria-lysosome contacts by GBA1 dysfunction in dopaminergic neuronal models of Parkinson’s disease," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    11. Radu Stoica & Kurt J. De Vos & Sébastien Paillusson & Sarah Mueller & Rosa M. Sancho & Kwok-Fai Lau & Gema Vizcay-Barrena & Wen-Lang Lin & Ya-Fei Xu & Jada Lewis & Dennis W. Dickson & Leonard Petrucel, 2014. "ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
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