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dc.contributor.authorKarniely, S
dc.contributor.authorWeekes, M
dc.contributor.authorAntrobus, R
dc.contributor.authorRorbach, J
dc.contributor.authorvan Haute, L
dc.contributor.authorUmrania, Y
dc.contributor.authorSmith, Duncan L
dc.contributor.authorStanton, R
dc.contributor.authorMinczuk, M
dc.contributor.authorLehner, P
dc.contributor.authorSinclair, J
dc.date.accessioned2016-04-22T15:06:59Zen
dc.date.available2016-04-22T15:06:59Zen
dc.date.issued2016en
dc.identifier.citationHuman Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries. 2016, 7 (2): mBioen
dc.identifier.issn2150-7511en
dc.identifier.pmid27025248en
dc.identifier.doi10.1128/mBio.00029-16en
dc.identifier.urihttp://hdl.handle.net/10541/606643en
dc.description.abstractInfection 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.
dc.language.isoenen
dc.rightsArchived with thanks to mBioen
dc.titleHuman cytomegalovirus infection upregulates the mitochondrial transcription and translation machineries.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine, University of Cambridge Clinical School, Addenbrookes Hospital, Cambridgeen
dc.identifier.journalmBioen
html.description.abstractInfection 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.


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