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Special Issue "Viruses and Cellular Metabolism"

A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (31 January 2019)

Special Issue Editor

Guest Editor
Dr. Rushika Perera

Arthropod-borne & Infectious Diseases Laboratory, Dept. of Microbiology, Immunology, and Pathology, Colorado State University, USA
Website | E-Mail
Interests: arboviral replication; cellular metabolism

Special Issue Information

Dear Colleagues,

Viruses are obligate pathogens; they therefore hijack host resources to complete their life cycle. Specifically, during infection of their hosts, viruses redirect normal cellular communication pathways such that attention is focused on efficient viral replication and virion biogenesis. The key effectors of cellular communication are metabolites that are intermediates or end products of biochemical reactions. Therefore, during infection, many viruses either stimulate or suppress several biochemical pathways such that metabolic intermediates and products solely support the success of the viral life cycle. In these events, select metabolic biosignatures of infection are also produced that could aid in the diagnoses of early disease manifestations.

The goal of this Special Issue on ‘Viruses and Cellular Metabolism’ is to highlight recent advances in our understanding of how viruses hijack cellular metabolic pathways for their benefit and how the host might metabolically counteract these processes. Invited are structural and functional studies that interrogate specific virus–host interactions that drive alterations in intracellular membrane organization and vesicular traffic, immunometabolism, central carbon, amino acid, and nucleotide and lipid metabolism. Studies on defining unique metabolic biosignatures for early triaging, treatment, and management of viral diseases are also invited.

Through this Special Issue, we hope to provide a current and comprehensive understanding of the role of metabolism in viral diseases, highlight emerging technologies and approaches important for studying disease-focused metabolism, understand how knowledge gained through these studies can be translated into antiviral interventions, and create a platform for the formulation of new hypotheses and collaborations.

Dr. Rushika Perera
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Review

Open AccessReview
Meal for Two: Human Cytomegalovirus-Induced Activation of Cellular Metabolism
Viruses 2019, 11(3), 273; https://doi.org/10.3390/v11030273
Received: 13 February 2019 / Revised: 12 March 2019 / Accepted: 13 March 2019 / Published: 19 March 2019
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Abstract
Viruses are parasites that depend on the host cell’s metabolic resources to provide the energy and molecular building blocks necessary for the production of viral progeny. It has become increasingly clear that viruses extensively modulate the cellular metabolic network to support productive infection. [...] Read more.
Viruses are parasites that depend on the host cell’s metabolic resources to provide the energy and molecular building blocks necessary for the production of viral progeny. It has become increasingly clear that viruses extensively modulate the cellular metabolic network to support productive infection. Here, we review the numerous ways through which human cytomegalovirus (HCMV) modulates cellular metabolism, highlighting known mechanisms of HCMV-mediated metabolic manipulation and identifying key outstanding questions that remain to be addressed. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
Metabolomic Insights into Human Arboviral Infections: Dengue, Chikungunya, and Zika Viruses
Viruses 2019, 11(3), 225; https://doi.org/10.3390/v11030225
Received: 31 January 2019 / Revised: 21 February 2019 / Accepted: 21 February 2019 / Published: 6 March 2019
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Abstract
The global burden of arboviral diseases and the limited success in controlling them calls for innovative methods to understand arbovirus infections. Metabolomics has been applied to detect alterations in host physiology during infection. This approach relies on mass spectrometry or nuclear magnetic resonance [...] Read more.
The global burden of arboviral diseases and the limited success in controlling them calls for innovative methods to understand arbovirus infections. Metabolomics has been applied to detect alterations in host physiology during infection. This approach relies on mass spectrometry or nuclear magnetic resonance spectroscopy to evaluate how perturbations in biological systems alter metabolic pathways, allowing for differentiation of closely related conditions. Because viruses heavily depend on host resources and pathways, they present unique challenges for characterizing metabolic changes. Here, we review the literature on metabolomics of arboviruses and focus on the interpretation of identified molecular features. Metabolomics has revealed biomarkers that differentiate disease states and outcomes, and has shown similarities in metabolic alterations caused by different viruses (e.g., lipid metabolism). Researchers investigating such metabolomic alterations aim to better understand host–virus dynamics, identify diagnostically useful molecular features, discern perturbed pathways for therapeutics, and guide further biochemical research. This review focuses on lessons derived from metabolomics studies on samples from arbovirus-infected humans. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
Influenza Virus Infections and Cellular Kinases
Viruses 2019, 11(2), 171; https://doi.org/10.3390/v11020171
Received: 4 January 2019 / Revised: 13 February 2019 / Accepted: 14 February 2019 / Published: 20 February 2019
Cited by 1 | PDF Full-text (592 KB) | HTML Full-text | XML Full-text
Abstract
Influenza A viruses (IAVs) are a major cause of respiratory illness and are responsible for yearly epidemics associated with more than 500,000 annual deaths globally. Novel IAVs may cause pandemic outbreaks and zoonotic infections with, for example, highly pathogenic avian influenza virus (HPAIV) [...] Read more.
Influenza A viruses (IAVs) are a major cause of respiratory illness and are responsible for yearly epidemics associated with more than 500,000 annual deaths globally. Novel IAVs may cause pandemic outbreaks and zoonotic infections with, for example, highly pathogenic avian influenza virus (HPAIV) of the H5N1 and H7N9 subtypes, which pose a threat to public health. Treatment options are limited and emergence of strains resistant to antiviral drugs jeopardize this even further. Like all viruses, IAVs depend on host factors for every step of the virus replication cycle. Host kinases link multiple signaling pathways in respond to a myriad of stimuli, including viral infections. Their regulation of multiple response networks has justified actively targeting cellular kinases for anti-cancer therapies and immune modulators for decades. There is a growing volume of research highlighting the significant role of cellular kinases in regulating IAV infections. Their functional role is illustrated by the required phosphorylation of several IAV proteins necessary for replication and/or evasion/suppression of the innate immune response. Identified in the majority of host factor screens, functional studies further support the important role of kinases and their potential as host restriction factors. PKC, ERK, PI3K and FAK, to name a few, are kinases that regulate viral entry and replication. Additionally, kinases such as IKK, JNK and p38 MAPK are essential in mediating viral sensor signaling cascades that regulate expression of antiviral chemokines and cytokines. The feasibility of targeting kinases is steadily moving from bench to clinic and already-approved cancer drugs could potentially be repurposed for treatments of severe IAV infections. In this review, we will focus on the contribution of cellular kinases to IAV infections and their value as potential therapeutic targets. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection
Viruses 2019, 11(2), 141; https://doi.org/10.3390/v11020141
Received: 11 January 2019 / Revised: 2 February 2019 / Accepted: 3 February 2019 / Published: 8 February 2019
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism
Viruses 2019, 11(2), 119; https://doi.org/10.3390/v11020119
Received: 3 January 2019 / Revised: 25 January 2019 / Accepted: 26 January 2019 / Published: 29 January 2019
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Abstract
Viruses manipulate numerous host factors and cellular pathways to facilitate the replication of viral genomes and the production of infectious progeny. One way in which viruses interact with cells is through the utilization and exploitation of the host lipid metabolism. While it is [...] Read more.
Viruses manipulate numerous host factors and cellular pathways to facilitate the replication of viral genomes and the production of infectious progeny. One way in which viruses interact with cells is through the utilization and exploitation of the host lipid metabolism. While it is likely that most—if not all—viruses require lipids or intermediates of lipid synthesis to replicate, many viruses also actively induce lipid metabolic pathways to sustain a favorable replication environment. From the formation of membranous replication compartments, to the generation of ATP or protein modifications, viruses exhibit differing requirements for host lipids. Thus, while the exploitation of lipid metabolism is a common replication strategy, diverse viruses employ a plethora of mechanisms to co-opt these critical cellular pathways. Here, we review recent literature regarding the exploitation of host lipids and lipid metabolism specifically by DNA viruses. Importantly, furthering the understanding of the viral requirements for host lipids may offer new targets for antiviral therapeutics and provide opportunities to repurpose the numerous FDA-approved compounds targeting lipid metabolic pathways as antiviral agents. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
Role of Host Cell Secretory Machinery in Zika Virus Life Cycle
Viruses 2018, 10(10), 559; https://doi.org/10.3390/v10100559
Received: 26 September 2018 / Revised: 11 October 2018 / Accepted: 12 October 2018 / Published: 15 October 2018
Cited by 2 | PDF Full-text (1257 KB) | HTML Full-text | XML Full-text
Abstract
The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat. The development of an effective vaccine against Zika virus may be [...] Read more.
The high human cost of Zika virus infections and the rapid establishment of virus circulation in novel areas, including the United States, present an urgent need for countermeasures against this emerging threat. The development of an effective vaccine against Zika virus may be problematic because of the cross reactivity of the antibodies with other flaviviruses leading to antibody-dependent enhancement of infection. Moreover, rapidly replicating positive strand RNA viruses, including Zika virus, generate large spectrum of mutant genomes (quasi species) every replication round, allowing rapid selection of variants resistant to drugs targeting virus-specific proteins. On the other hand, viruses are ultimate cellular parasites and rely on the host metabolism for every step of their life cycle, thus presenting an opportunity to manipulate host processes as an alternative approach to suppress virus replication and spread. Zika and other flaviviruses critically depend on the cellular secretory pathway, which transfers proteins and membranes from the ER through the Golgi to the plasma membrane, for virion assembly, maturation and release. In this review, we summarize the current knowledge of interactions of Zika and similar arthropod-borne flaviviruses with the cellular secretory machinery with a special emphasis on virus-specific changes of the secretory pathway. Identification of the regulatory networks and effector proteins required to accommodate the trafficking of virions, which represent a highly unusual cargo for the secretory pathway, may open an attractive and virtually untapped reservoir of alternative targets for the development of superior anti-viral drugs. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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Open AccessReview
A Systems Approach to Study Immuno- and Neuro-Modulatory Properties of Antiviral Agents
Viruses 2018, 10(8), 423; https://doi.org/10.3390/v10080423
Received: 26 July 2018 / Revised: 10 August 2018 / Accepted: 11 August 2018 / Published: 12 August 2018
Cited by 1 | PDF Full-text (4832 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo [...] Read more.
There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which may be associated with potential side effects of these therapeutics. The current approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by mRNA, cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties. Full article
(This article belongs to the Special Issue Viruses and Cellular Metabolism)
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