scholarly journals Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 141 ◽  
Author(s):  
Martin A. Prusinkiewicz ◽  
Joe S. Mymryk
Keyword(s):  
Viral Replication ◽  
Viral Infections ◽  
Cellular Metabolism ◽  
Human Adenovirus ◽  
Metabolic Reprogramming ◽  
Cancer Treatments ◽  
Cellular Processes ◽  
Intracellular Parasites ◽  
Tumor Virus ◽  
Altered Metabolism

Viruses are obligate intracellular parasites that alter many cellular processes to create an environment optimal for viral replication. Reprogramming of cellular metabolism is an important, yet underappreciated feature of many viral infections, as this ensures that the energy and substrates required for viral replication are available in abundance. Human adenovirus (HAdV), which is the focus of this review, is a small DNA tumor virus that reprograms cellular metabolism in a variety of ways. It is well known that HAdV infection increases glucose uptake and fermentation to lactate in a manner resembling the Warburg effect observed in many cancer cells. However, HAdV infection induces many other metabolic changes. In this review, we integrate the findings from a variety of proteomic and transcriptomic studies to understand the subtleties of metabolite and metabolic pathway control during HAdV infection. We review how the E4ORF1 protein of HAdV enacts some of these changes and summarize evidence for reprogramming of cellular metabolism by the viral E1A protein. Therapies targeting altered metabolism are emerging as cancer treatments, and similar targeting of aberrant components of virally reprogrammed metabolism could have clinical antiviral applications.

scholarly journals Sphingolipids: Effectors and Achilles Heals in Viral Infections?

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2175
Author(s):  
Sibylle Schneider-Schaulies ◽  
Fabian Schumacher ◽  
Dominik Wigger ◽  
Marie Schöl ◽  
Trushnal Waghmare ◽  
...  
Keyword(s):  
Life Cycle ◽  
Viral Replication ◽  
Viral Infections ◽  
Cellular Level ◽  
Host Cells ◽  
Cellular Membranes ◽  
Replication Process ◽  
Intracellular Parasites ◽  
Intracellular Compartments ◽  
Cellular Components

As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.

scholarly journals Cell Biology of Viral Infections

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2431
Author(s):  
Pierre-Yves Lozach
Keyword(s):  
Host Cell ◽  
Cell Biology ◽  
Viral Infections ◽  
Life Forms ◽  
Original Research ◽  
Cellular Processes ◽  
Intracellular Parasites ◽  
Technological Developments ◽  
Life Threatening ◽  
Host Cell Interactions

Viruses exhibit an elegant simplicity, as they are so basic, but so frightening. Although only a few are life threatening, they have substantial implications for human health and the economy, as exemplified by the ongoing coronavirus pandemic. Viruses are rather small infectious agents found in all types of life forms, from animals and plants to prokaryotes and archaebacteria. They are obligate intracellular parasites, and as such, subvert many molecular and cellular processes of the host cell to ensure their own replication, amplification, and subsequent spread. This special issue addresses the cell biology of viral infections based on a collection of original research articles, communications, opinions, and reviews on various aspects of virus-host cell interactions. Together, these articles not only provide a glance into the latest research on the cell biology of viral infections, but also include novel technological developments.

scholarly journals Oligonucleotide-Based Approaches to Inhibit Dengue Virus Replication

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 956
Author(s):  
Kingshuk Panda ◽  
Kalichamy Alagarasu ◽  
Deepti Parashar
Keyword(s):  
Dengue Virus ◽  
Viral Replication ◽  
Viral Infections ◽  
Public Health Problem ◽  
Denv Infection ◽  
Viral Rna ◽  
Effective Vaccine ◽  
Cellular Processes ◽  
Antiviral Therapies ◽  
Life Threatening

Dengue fever is one of the most common viral infections affecting humans. It is an expanding public health problem, particularly in tropical and subtropical regions. No effective vaccine or antiviral therapies against Dengue virus (DENV) infection are available. Therefore, there is a strong need to develop safe and effective therapeutic strategies that can reduce the burden and duration of hospitalizations due to this life-threatening disease. Oligonucleotide-based strategies are considered as an attractive means of inhibiting viral replication since oligonucleotides can be designed to interact with any viral RNA, provided its sequence is known. The resultant targeted destruction of viral RNA interferes with viral replication without inducing any adverse effects on cellular processes. In this review, we elaborate the ribozymes, RNA interference, CRISPR, aptamer and morpholino strategies for the inhibition of DENV replication and discuss the challenges involved in utilizing such approaches.

scholarly journals Redox Regulation of Lipid Mobilization in Adipose Tissues

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1090
Author(s):  
Ursula Abou-Rjeileh ◽  
G. Andres Contreras
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Redox Regulation ◽  
Cellular Metabolism ◽  
Antioxidant Response ◽  
Redox Signaling ◽  
Nitrogen Species ◽  
Adipose Tissues ◽  
Lipid Mobilization ◽  
Cellular Processes

Lipid mobilization in adipose tissues, which includes lipogenesis and lipolysis, is a paramount process in regulating systemic energy metabolism. Reactive oxygen and nitrogen species (ROS and RNS) are byproducts of cellular metabolism that exert signaling functions in several cellular processes, including lipolysis and lipogenesis. During lipolysis, the adipose tissue generates ROS and RNS and thus requires a robust antioxidant response to maintain tight regulation of redox signaling. This review will discuss the production of ROS and RNS within the adipose tissue, their role in regulating lipolysis and lipogenesis, and the implications of antioxidants on lipid mobilization.

scholarly journals Escaping KRAS: Gaining Autonomy and Resistance to KRAS Inhibition in KRAS Mutant Cancers

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5081
Author(s):  
Yuta Adachi ◽  
Ryo Kimura ◽  
Kentaro Hirade ◽  
Hiromichi Ebi
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Acquired Resistance ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Activating Mutations ◽  
Survival Signaling ◽  
Kras Protein ◽  
Effector Pathways ◽  
Specific Inhibitors

Activating mutations in KRAS are present in 25% of human cancers. When mutated, the KRAS protein becomes constitutively active, stimulating various effector pathways and leading to the deregulation of key cellular processes, including the suppression of apoptosis and enhancement of proliferation. Furthermore, mutant KRAS also promotes metabolic deregulation and alterations in the tumor microenvironment. However, some KRAS mutant cancer cells become independent of KRAS for their survival by activating diverse bypass networks that maintain essential survival signaling originally governed by mutant KRAS. The proposed inducers of KRAS independency are the activation of YAP1 and/or RSK-mTOR pathways and co-mutations in SKT11 (LKB1), KEAP1, and NFE2L2 (NRF2) genes. Metabolic reprogramming, such as increased glutaminolysis, is also associated with KRAS autonomy. The presence or absence of KRAS dependency is related to the heterogeneity of KRAS mutant cancers. Epithelial-to-mesenchymal transition (EMT) in tumor cells is also a characteristic phenotype of KRAS independency. Translationally, this loss of dependence is a cause of primary and acquired resistance to mutant KRAS-specific inhibitors. While KRAS-dependent tumors can be treated with mutant KRAS inhibitor monotherapy, for KRAS-independent tumors, we need an improved understanding of activated bypass signaling pathways towards leveraging vulnerabilities, and advancing therapeutic options for this patient subset.

scholarly journals Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Kingsley Gideon Kumashie ◽  
Marcin Cebula ◽  
Claudia Hagedorn ◽  
Florian Kreppel ◽  
Marina C. Pils ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Cell Formation ◽  
T Cell Response ◽  
Cellular Processes ◽  
Metabolic Functions ◽  
Cpg Oligonucleotide ◽  
Novel Approach

Chronic hepatotropic viral infections are characterized by exhausted CD8+ T cells in the presence of cognate antigen in the liver. The impairment of T cell response limits the control of chronic hepatotropic viruses. Immune-modulatory strategies are attractive options to re-invigorate exhausted T cells. However, in hepatotropic viral infections, the knowledge about immune-modulatory effects on the in-situ regulation of exhausted intrahepatic CD8+ T cells is limited. In this study, we elucidated the functional heterogeneity in the pool of exhausted CD8+ T cells in the liver of mice expressing the model antigen Ova in a fraction of hepatocytes. We found a subpopulation of intrahepatic CXCR5+ Ova-specific CD8+ T cells, which are profoundly cytotoxic, exhibiting efficient metabolic functions as well as improved memory recall and self-maintenance. The intrahepatic Ova-specific CXCR5+ CD8+ T cells are possibly tissue resident cells, which may rely largely on OXPHOS and glycolysis to fuel their cellular processes. Importantly, host conditioning with CpG oligonucleotide reinvigorates and promotes exhausted T cell expansion, facilitating complete antigen eradication. The CpG oligonucleotide-mediated reinvigoration may support resident memory T cell formation and the maintenance of CXCR5+ Ova-specific CD8+ T cells in the liver. These findings suggest that CpG oligodinucleotide may preferentially target CXCR5+ CD8+ T cells for expansion to facilitate the revival of exhausted T cells. Thus, therapeutic strategies aiming to expand CXCR5+ CD8+ T cells might provide a novel approach against chronic liver infection.

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

scholarly journals Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

2020 ◽  
Vol 11 ◽  
Author(s):  
Shubhranshu S. Gupta ◽  
Jin Wang ◽  
Min Chen
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Viral Infections ◽  
Metabolic Reprogramming

scholarly journals The SMC5/6 Complex Represses the Replicative Program of High-Risk Human Papillomavirus Type 31

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 786
Author(s):  
Ryan T. Gibson ◽  
Elliot J. Androphy
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Viral Replication ◽  
Chromatin Immunoprecipitation ◽  
Binding Sites ◽  
Viral Infections ◽  
Hpv Infection ◽  
Regulatory Proteins ◽  
Transactivation Domain ◽  
Structural Maintenance Of Chromosomes

The multi-subunit structural maintenance of chromosomes (SMC) 5/6 complex includes SMC6 and non-SMC element (NSE)3. SMC5/6 is essential for homologous recombination DNA repair and functions as an antiviral factor during hepatitis B (HBV) and herpes simplex-1 (HSV-1) viral infections. Intriguingly, SMC5/6 has been found to associate with high-risk human papillomavirus (HPV) E2 regulatory proteins, but the functions of this interaction and its role during HPV infection remain unclear. Here, we further characterize SMC5/6 interactions with HPV-31 E2 and its role in the HPV life cycle. Co-immunoprecipitation (co-IP) revealed that SMC6 interactions with HPV-31 E2 require the E2 transactivation domain, implying that SMC5/6 interacts with full-length E2. Using chromatin immunoprecipitation, we found that SMC6 is present on HPV-31 episomes at E2 binding sites. The depletion of SMC6 and NSE3 increased viral replication and transcription in keratinocytes maintaining episomal HPV-31, indicating that SMC5/6 restricts the viral replicative program. SMC6 interactions with E2 were reduced in the presence of HPV-31 E1, suggesting that SMC6 and E1 compete for E2 binding. Our findings demonstrate SMC5/6 functions as a repressor of the viral replicative program and this may involve inhibiting the initiation of viral replication.

scholarly journals MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2525
Author(s):  
Jorlan Fernandes ◽  
Renan Lyra Miranda ◽  
Elba Regina Sampaio de Lemos ◽  
Alexandro Guterres
Keyword(s):  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Mirna Expression Profile ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Emerging Viruses ◽  
Cellular Mirnas ◽  
Host Interactions ◽  
Causative Agents

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

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