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    Human cytomegalovirus infection upregulates the mitochondrial transcription and translation machineries.

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    Authors
    Karniely, S
    Weekes, M
    Antrobus, R
    Rorbach, J
    van Haute, L
    Umrania, Y
    Smith, Duncan L
    Stanton, R
    Minczuk, M
    Lehner, P
    Sinclair, J
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    Affiliation
    Department of Medicine, University of Cambridge Clinical School, Addenbrookes Hospital, Cambridge
    Issue Date
    2016
    
    Metadata
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    Abstract
    Infection with human cytomegalovirus (HCMV) profoundly affects cellular metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose carbon is shifted from the mitochondrial tricarboxylic acid cycle to the biosynthesis of fatty acids. However, unlike in many tumor cells, where aerobic glycolysis is accompanied by suppression of mitochondrial oxidative phosphorylation, HCMV induces mitochondrial biogenesis and respiration. Here, we affinity purified mitochondria and used quantitative mass spectrometry to determine how the mitochondrial proteome changes upon HCMV infection. We found that the mitochondrial transcription and translation systems are induced early during the viral replication cycle. Specifically, proteins involved in biogenesis of the mitochondrial ribosome were highly upregulated by HCMV infection. Inhibition of mitochondrial translation with chloramphenicol or knockdown of HCMV-induced ribosome biogenesis factor MRM3 abolished the HCMV-mediated increase in mitochondrially encoded proteins and significantly impaired viral growth under bioenergetically restricting conditions. Our findings demonstrate how HCMV manipulates mitochondrial biogenesis to support its replication.
    Citation
    Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries. 2016, 7 (2): mBio
    Journal
    mBio
    URI
    http://hdl.handle.net/10541/606643
    DOI
    10.1128/mBio.00029-16
    PubMed ID
    27025248
    Type
    Article
    Language
    en
    ISSN
    2150-7511
    ae974a485f413a2113503eed53cd6c53
    10.1128/mBio.00029-16
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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