Human cytomegalovirus infection upregulates the mitochondrial transcription and translation machineries

Karniely, S., Weekes, M. P., Antrobus, R., Rorbach, J., van Haute, L., Umrania, Y., Smith, D. L., Stanton, Richard James ORCID: https://orcid.org/0000-0002-6799-1182, Minczuk, M., Lehner, P. J. and Sinclair, J. H. 2016. Human cytomegalovirus infection upregulates the mitochondrial transcription and translation machineries. mBio 7 (2) , e00029-16. 10.1128/mBio.00029-16

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR355 Virology
Publisher:	American Society for Microbiology
ISSN:	2150-7511
Date of First Compliant Deposit:	11 April 2016
Date of Acceptance:	25 February 2016
Last Modified:	05 May 2023 13:56
URI:	https://orca.cardiff.ac.uk/id/eprint/89016

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