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Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection

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  • Yutaka Hashimoto

    (Princeton University, Lewis Thomas Laboratory
    National Institute for Basic Biology
    International Research Collaboration Center, National Institutes of Natural Sciences
    Department of Cell Biology, Nagoya City University Graduate School of Medicine Sciences)

  • Xinlei Sheng

    (Princeton University, Lewis Thomas Laboratory)

  • Laura A. Murray-Nerger

    (Princeton University, Lewis Thomas Laboratory)

  • Ileana M. Cristea

    (Princeton University, Lewis Thomas Laboratory)

Abstract

The co-evolution and co-existence of viral pathogens with their hosts for millions of years is reflected in dynamic virus-host protein-protein interactions (PPIs) that are intrinsic to the spread of infections. Here, we investigate the system-wide dynamics of protein complexes throughout infection with the herpesvirus, human cytomegalovirus (HCMV). Integrating thermal shift assays and mass spectrometry quantification with virology and microscopy, we monitor the temporal formation and dissociation of hundreds of functional protein complexes and the dynamics of host-host, virus-host, and virus-virus PPIs. We establish pro-viral roles for cellular protein complexes and translocating proteins. We show the HCMV receptor integrin beta 1 dissociates from extracellular matrix proteins, becoming internalized with CD63, which is necessary for virus production. Moreover, this approach facilitates characterization of essential viral proteins, such as pUL52. This study of temporal protein complex dynamics provides insights into mechanisms of HCMV infection and a resource for biological and therapeutic studies.

Suggested Citation

  • Yutaka Hashimoto & Xinlei Sheng & Laura A. Murray-Nerger & Ileana M. Cristea, 2020. "Temporal dynamics of protein complex formation and dissociation during human cytomegalovirus infection," Nature Communications, Nature, vol. 11(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14586-5
    DOI: 10.1038/s41467-020-14586-5
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    Cited by:

    1. Andrea Fossati & Deepto Mozumdar & Claire Kokontis & Melissa Mèndez-Moran & Eliza Nieweglowska & Adrian Pelin & Yuping Li & Baron Guo & Nevan J. Krogan & David A. Agard & Joseph Bondy-Denomy & Daniell, 2023. "Next-generation proteomics for quantitative Jumbophage-bacteria interaction mapping," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Siyuan Sun & Zhenxiang Zheng & Jun Wang & Fengming Li & An He & Kunjia Lai & Shuang Zhang & Jia-Hong Lu & Ruijun Tian & Chris Soon Heng Tan, 2023. "Improved in situ characterization of protein complex dynamics at scale with thermal proximity co-aggregation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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