Progression of herpesvirus infection remodels mitochondrial organization and metabolism

Simon Leclerc, Alka Gupta, Visa Ruokolainen, Jian-Hua Chen, Kari Kunnas, Axel A Ekman, Henri Niskanen, Ilya Belevich, Helena Vihinen, Paula Turkki, Ana J Perez-Berna, Sergey Kapishnikov, Elina Mäntylä, Maria Harkiolaki, Eric Dufour, Vesa Hytönen, Eva Pereiro, Tony McEnroe, Kenneth Fahy, Minna U KaikkonenEija Jokitalo, Carolyn A Larabell, Venera Weinhardt, Salla Mattola, Vesa Aho, Maija Vihinen-Ranta

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

Original languageEnglish
Article numbere1011829
JournalPLOS PATHOGENS
Volume20
Issue number4
DOIs
Publication statusE-pub ahead of print - 15 Apr 2024
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 3

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