Structural changes

Structural changes and protein-protein interactions

Chromatin

During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. HSV-1 infection induces the formation of channels through the peripheral chromatin layer. The random walk modeling chromatin reconstruction indicated a gradually faster transport of capsids to the nuclear envelope that correlated with increased interchromatin channels in the nuclear periphery.

Publications

Chen JH, Vanslembrouck B, Ekman A, Aho V, Larabell CA, Le Gros MA, Vihinen-Ranta M, Weinhardt V (2022). Soft X-ray Tomography Reveals HSV-1-Induced Remodeling of Human B Cells. Viruses14: 2651.

Fahy K, Weinhardt V, Vihinen-Ranta M, Skoko D, Fletcher E, Scholz D, Bartenschlager R, Ekman A, Gastaminza P, Pereiro E, McEnroe T (2021). Compact Cell Imaging Device – to provide insights into the cellular origins of viral diseases. J Phys Photonics 3(3):031002.

Aho V, Mäntylä E, Ekman A, Hakanen S, Mattola S, Chen J-H, S, Weinhardt V, Ruokolainen V, Sodeik B, Larabell CA, and Vihinen-Ranta M (2019). Quantitative microscopy reveals stepwise alteration of chromatin structure during herpesvirus infection. Viruses, 11 (10): 935.

AhoV, Myllys M, LarabellCA, Vihinen-RantaM (2017). Chromatin Reorganization during Viral Infection. Microscopy and Microanalysis 23(S1): 988.

Myllys M, Ruokolainen V,Aho V, Smith E, Hakanen S, Peri P,Salvetti A, Timonen J Hukkanen V,Larabell C,and Vihinen-Ranta M (2016).Herpes simplex virus 1 induces egress channels through marginalized host chromatin. Sci Rep 6: 28844.

Nucleoli

We examine the mechanisms of virus-induced changes in nucleolar structure, function, and dynamics. Specifically, we are interested in infection-induced changes in the structure of the nucleolus, the organization of chromatin, and nucleolar proteins.

Publications

Mattola S, Leclerc S, Hakanen S, Huttunen M, Aho, V, Parrish, CR, Vihinen-Ranta M(2023), Parvovirus infection alters the nucleolar structure. bioRxiv 2022.06.07.495090.

Mitochondria

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. We have shown 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 at the perinuclear area, a significant increase in the number and clustering of ER-mitochondria contact sites, thickening and shortening of mitochondrial cristae. Our 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.

Publications

Simon Leclerc, Alka Gupta, Visa Ruokolainen,Jian-Hua Chen, Kari Kunna, Axel A. Ekman, Henri Niskanen, Ilya Belevich, Helena Vihinen, Paula Turkk, Ana J. Perez-Berna, Sergey Kapishnikov, Elina Mäntylä, Maria Harkiolaki, Eric Dufour, Vesa Hytönen, Eva Pereiro, Tony McEnroe, Kenneth Fahy, Minna U. Kaikkonen, Eija Jokitalo, Carolyn A. Larabell, Venera Weinhardt, Salla Mattola, Vesa Aho, Maija Vihinen-Ranta(2023). Progression of herpesvirus infection remodels mitochondrial organization and metabolism. bioRxiv 2023.11.16.567337. PloS Pathogens, in revision.