Mitochondrial Proteins Coded by Human Tumor Viruses

Cavallari, Ilaria; Scattolin, Gloria; Silic-Benussi, Micol; Raimondi, Vittoria; D’Agostino, Donna M.; Ciminale, Vincenzo

doi:10.3389/fmicb.2018.00081

Cited by 14 publications

(18 citation statements)

References 169 publications

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“…Given the importance of mitochondria in anti-viral innate immunity, it will also be important to discover if, by targeting mitochondria, p13 may hamper the host cell's anti-viral responses. Notably, several other human tumor viruses also code for mitochondrial proteins, with diverse effects on mitochondrial function and the viral life cycle [56].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies over the past decade have revealed important roles for mitochondria in immune responses [53]. Many viruses encode mitochondrial proteins that are important for viral spread and persistence [54][55][56], and several viruses target MAVS (mitochondrial antiviralsignaling protein), a cellular protein localized in the outer mitochondrial membrane, mitochondrial-associated membranes, and peroxisomes that plays a critical role in innate immune response against RNA viruses [57][58][59]. The ability of HTLV-1 to infect monocytes suggests that the virus might impinge on the host's innate immune responses [60][61][62][63].…”

Section: P13 and The Host Immune Responsementioning

confidence: 99%

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Functional properties and sequence variation of HTLV-1 p13

et al. 2020

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Human T cell leukemia virus type-1 (HTLV-1) was the first retrovirus found to cause cancer in humans, but the mechanisms that drive the development of leukemia and other diseases associated with HTLV-1 infection remain to be fully understood. This review describes the functional properties of p13, an 87-amino acid protein coded by HTLV-1 open reading frame II (orf-II). p13 is mainly localized in the inner membrane of the mitochondria, where it induces potassium (K +) influx and reactive oxygen species (ROS) production, which can trigger either proliferation or apoptosis, depending on the ROS setpoint of the cell. Recent evidence indicates that p13 may influence the cell's innate immune response to viral infection and the infected cell phenotype. Association of the HTLV-1 transcriptional activator, Tax, with p13 increases p13's stability, leads to its partial co-localization with Tax in nuclear speckles, and reduces the ability of Tax to interact with the transcription cofactor CBP/p300. Comparison of p13 sequences isolated from HTLV-1-infected individuals revealed a small number of amino acid variations in the domains controlling the subcellular localization of the protein. Disruptive mutations of p13 were found in samples obtained from asymptomatic patients with low proviral load. p13 sequences of HTLV-1 subtype C isolates from indigenous Australian patients showed a high degree of identity among each other, with all samples containing a pattern of 5 amino acids that distinguished them from other subtypes. Further characterization of p13's functional properties and sequence variants may lead to a deeper understanding of the impact of p13 as a contributor to the clinical manifestations of HTLV-1 infection.

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Section: Discussionmentioning

confidence: 99%

Section: P13 and The Host Immune Responsementioning

confidence: 99%

Functional properties and sequence variation of HTLV-1 p13

et al. 2020

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“…The Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and encodes an 87-amino acid protein (p13) that helps this virus to establish a persistent infection. This protein primarily accumulates in the inner mitochondrial membrane of host cells and alters mitochondrial morphology toward a more rounded shape, fragments mitochondria (mitochondrial fission), and reduces mitochondrial Ca 2+ uptake (Biasiotto et al, 2010; Cavallari et al, 2018).…”

Section: Mitochondrial Proteins Other Than Mavs As Targets Of Viral Imentioning

confidence: 99%

“…Several proteins encoded by Epstein Barr virus (EBV) target mitochondria, such as BHRF1 (BamHI-H right reading frame), BZLF1 (also known as Zebra protein), BALF1 (BamHI-A left frame transcript), LMP2A (Latent membrane protein), and immediate early Zta protein. BHRF1 accumulates in the outer mitochondrial membrane (OMM) of B lymphocytes, preventing apoptosis and promoting survival of EBV-infected cells, viral persistence, and replication; BHRF presents homology with the transmembrane domains of some eukaryotic Bcl-2 family members (Kvansakul et al, 2017; Cavallari et al, 2018); and BZLF1 has the capacity to interact with mtSSB (mitochondrial single-stranded DNA-binding protein), which is required for the replication of the mitochondrial genome, and partially redirects mtSSB from mitochondria to the nucleus (LaJeunesse et al, 2005; Cavallari et al, 2018). BALF1 also shares homology with Bcl-2 family members and modulates apoptosis and promotes transformation (Hsu et al, 2012; Cavallari et al, 2018).…”

Section: Mitochondrial Proteins Other Than Mavs As Targets Of Viral Imentioning

confidence: 99%

Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses

Moreno-Altamirano

Kolstoe

Sánchez‐García

2019

Front. Cell. Infect. Microbiol.

104

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Over the last decade, there has been significant advances in the understanding of the cross-talk between metabolism and immune responses. It is now evident that immune cell effector function strongly depends on the metabolic pathway in which cells are engaged in at a particular point in time, the activation conditions, and the cell microenvironment. It is also clear that some metabolic intermediates have signaling as well as effector properties and, hence, topics such as immunometabolism, metabolic reprograming, and metabolic symbiosis (among others) have emerged. Viruses completely rely on their host's cell energy and molecular machinery to enter, multiply, and exit for a new round of infection. This review explores how viruses mimic, exploit or interfere with host cell metabolic pathways and how, in doing so, they may evade immune responses. It offers a brief outline of key metabolic pathways, mitochondrial function and metabolism-related signaling pathways, followed by examples of the mechanisms by which several viral proteins regulate host cell metabolic activity.

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“…In the nucleus of epithelial cells, adenovirus E4 Orf1 uses Myc to induce glycolytic genes in a way that is striking enough to change the tissue culture medium from red to deep yellow in color [45]. Many viruses encode proteins or non-coding RNAs that target mitochondria [89][90][91][92]. When expressed without infection, KSHV microRNAs reduced the number of mitochondria causing the cell to switch from ATP production via oxidative phosphorylation to glucose conversion to lactate [93].…”

Section: Mechanisms Of Viral Metabolic Hijackingmentioning

confidence: 99%

Pathways to Understanding Virus-Host Metabolism Interactions

Purdy

2018

Curr Clin Micro Rpt

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Purpose of ReviewViruses have vast diversity in terms of virion structure, genomic content, and host. All viruses, however, rely on host metabolism as none encode a metabolic network. Although virus-host metabolism interactions are critical to infection, little is understood regarding viral remodeling of its host metabolic network. Likewise, for most viruses, we have yet to identify if and how viruses govern the activity of metabolic pathways. Fortunately, metabolic analyses are becoming more accessible to virologist, thanks in large part to advances in mass spectrometry-based approaches. A brief overview of virus-metabolism interactions and the current state-of-the-art approaches to metabolomics, lipidomics and metabolic analyses are discussed. Recent FindingsIn the last several years, multiple metabolomic and lipidomic studies during virus infection have been reported. Products of the metabolic network support or limit infection. When considering how viruses interact with host metabolism it is critical for virologist to think beyond their copy of a Biochemistry textbook, as computational and analytical advances in recent years have led to novel discoveries in metabolism. Some of those advances and discoveries are introduced here, with a focus on the recent finds in virus-host metabolism interactions.Summary Metabolism is important to viral infections beyond simply keeping a cell alive while the virus replicates. Recent advances in tools and methods to dissect metabolism during infection have led to novel findings in infection-induced changes in metabolism. Continued research is necessary to build comprehensive understanding of how viruses interact with their host's metabolic network.

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Mitochondrial Proteins Coded by Human Tumor Viruses

Cited by 14 publications

References 169 publications

Functional properties and sequence variation of HTLV-1 p13

Functional properties and sequence variation of HTLV-1 p13

Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses

Pathways to Understanding Virus-Host Metabolism Interactions

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