Mitochondrial distribution and function in herpes simplex virus-infected cells

Murata, Takayuki; Goshima, Fumi; Daikoku, Tohru; Inagaki–Ohara, Kyoko; Takakuwa, Hiroki; Kato, Keisuke; Nishiyama, Yukihiro

doi:10.1099/0022-1317-81-2-401

Cited by 98 publications

(105 citation statements)

References 23 publications

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“…21 A similar redistribution of mitochondria around the nucleus of infected neurons was demonstrated in the case of HSV infection accompanied by increased concentration of viral tegument proteins around the nucleus. 34 Interestingly, such a perinuclear clustering of mitochondria was also observed in fibroblasts obtained from Alzheimer's patients, suggestive of a relevance to neurodegenerative conditions. 35 We wanted to determine whether TC-83 infection led to alterations in the distribution of mitochondria in infected cells.…”

Section: Mitochondrial Distribution Is Altered In Tc-83 Infected U87mmentioning

confidence: 84%

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

et al. 2017

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Mitochondria are sentinel organelles that are impacted by various forms of cellular stress, including viral infections. While signaling events associated with mitochondria, including those activated by pathogen associated molecular patterns (PAMPs), are widely studied, alterations in mitochondrial distribution and changes in mitochondrial dynamics are also beginning to be associated with cellular insult. Cells of neuronal origin have been demonstrated to display remarkable alterations in several instances, including neurodegenerative disorders. Venezuelan Equine Encephalitis Virus (VEEV) is a New World alphavirus that infects neuronal cells and contributes to an encephalitic phenotype. We demonstrate that upon infection by the vaccine strain of VEEV (TC-83), astrocytoma cells experience a robust drop in mitochondrial activity, which corresponds with an increased accumulation of reactive oxygen species (ROS) in an infection-dependent manner. Infection status also corresponds with a prominent perinuclear accumulation of mitochondria. Cellular enzymatic machinery, including PINK1 and Parkin, appears to be enriched in mitochondrial fractions as compared with uninfected cells, which is indicative of mitochondrial damage. Dynamin related protein 1 (Drp1), a protein that is associated with mitochondrial fission, demonstrated a modest enrichment in mitochondrial fractions of infected cells. Treatment with an inhibitor of mitochondrial fission, Mdivi-1, led to a decrease in caspase cleavage, suggesting that mitochondrial fission was likely to contribute to apoptosis of infected cells. Finally, our data demonstrate that mitophagy ensues in infected cells. In combination, our data suggest that VEEV infection results in significant changes in the mitochondrial landscape that may influence pathological outcomes in the infected cell.

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Section: Mitochondrial Distribution Is Altered In Tc-83 Infected U87mmentioning

confidence: 84%

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

et al. 2017

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“…In addition to this accepted marker of mitochondrial stress, maintenance of the mitochondrial membrane potential (MMP) is also utilized as a marker of mitochondrial function [17,18,24,38]. We have shown that these two events correlate with increased mitochondrial fission and mitophagy, contributing to cell death in an infection dependent manner [24].…”

Section: Resultsmentioning

confidence: 99%

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

et al. 2018

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Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is highly infectious as an aerosol and can result in an encephalitic phenotype in infected individuals. VEEV infections are known to be associated with robust inflammation that eventually contributes to neurodegenerative phenotypes. In this study, we utilize the TC-83 strain of VEEV, which is known to induce the expression of IL-6, IL-8, and other pro-inflammatory cytokines. We had previously demonstrated that TC-83 infection resulted in changes in mitochondrial function, eventually resulting in mitophagy. In this manuscript, we provide data that links upstream mitochondrial dysfunction with downstream pro-inflammatory cytokine production in the context of microglia and astrocytoma cells. We also provide data on the role of bystander cells, which significantly contribute to the overall inflammatory load. Use of a mitochondrial-targeted antioxidant, mitoquinone mesylate, greatly reduced the inflammatory cytokine load and ameliorated bystander cell inflammatory responses more significantly than a broad-spectrum anti-inflammatory compound (BAY 11–7082). Our data suggest that the inflammatory mediators, especially IL-1β, may prime naïve cells to infection and lead to increased infection rates in microglial and astrocytoma cells. Cumulatively, our data suggest that the interplay between mitochondrial dysfunction and inflammatory events elicited in a neuronal microenvironment during a TC-83 infection may contribute to the spread of infection.

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“…Interestingly, significantly morphological changes of mitochondria also appear in the RGV-infected fish cells, and numerous dumbbell-shaped mitochondria are distributed around the viromatrix. Previous reports have indicated that changes of the mitochondrial distribution not only provide the energy for virus pathogenesis, but also play important roles in the process of apoptosis [26,27]. In the cases of the mammalian viruses, mitochondrial distribution changes and apoptosis occurrence have been observed during viral infection [28,29].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrion-mediated apoptosis induced by Rana grylio virus infection in fish cells

Huang

Gui

et al. 2007

Apoptosis

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A fish cell line, fathead minnow (FHM) cell, was used to investigate the alteration of mitochondrial dynamics and the mechanism of apoptosis under Rana grylio virus (RGV) infection. Microscopy observations, flow-cytometry analysis and molecular marker detection revealed the apoptotic fate of the RGV-infected cells. Some typical apoptotic characteristics, such as chromatin condensation, DNA fragmentation and mitochondrial fragmentation, were observed, and significantly morphological changes of mitochondria, including size, shape, internal structure and distribution, were revealed. The mitochondria in RGV-infected cells were aggregated around the viromatrix, and the aggregation could be blocked by colchicine. Moreover, the Dwm collapse was induced, and caspase-9 and caspase-3 were activated in the RGV-infected cells. In addition, NF-jB activation and intracellular Ca 2+ increase were also detected at different times after infection. The data revealed the detailed dynamics of mitochondrion-mediated apoptosis induced by an iridovirus, and provided the first report on mitochondrial fragmentation during virus-induced apoptosis in fish cells.

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Mitochondrial distribution and function in herpes simplex virus-infected cells

Cited by 98 publications

References 23 publications

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells

Mitochondrion-mediated apoptosis induced by Rana grylio virus infection in fish cells

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