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 Role of Lipid Transfer Proteins (LTPs) in the Viral Life Cycle

2021 ◽  
Vol 12 ◽  
Author(s):  
Kiran Avula ◽  
Bharati Singh ◽  
Preethy V. Kumar ◽  
Gulam H. Syed
Keyword(s):  
Life Cycle ◽  
Viral Replication ◽  
Host Cell ◽  
Lipid Membrane ◽  
Positive Curvature ◽  
Viral Life Cycle ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Flexible Form ◽  
Cellular Components

Viruses are obligate parasites that depend on the host cell machinery for their replication and dissemination. Cellular lipids play a central role in multiple stages of the viral life cycle such as entry, replication, morphogenesis, and egress. Most viruses reorganize the host cell membranes for the establishment of viral replication complex. These specialized structures allow the segregation of replicating viral RNA from ribosomes and protect it from host nucleases. They also facilitate localized enrichment of cellular components required for viral replication and assembly. The specific composition of the lipid membrane governs its ability to form negative or positive curvature and possess a rigid or flexible form, which is crucial for membrane rearrangement and establishment of viral replication complexes. In this review, we highlight how different viruses manipulate host lipid transfer proteins and harness their functions to enrich different membrane compartments with specific lipids in order to facilitate multiple aspects of the viral life cycle.

scholarly journals Phytochemicals: Potential Lead Compounds for COVID-19 Therapeutics

2021 ◽  
Vol 15 ◽  
Author(s):  
Srishti Kashyap ◽  
Revathy Nadhan ◽  
Danny N. Dhanasekaran
Keyword(s):  
Life Cycle ◽  
Viral Replication ◽  
Viral Infection ◽  
Viral Entry ◽  
Fatal Outcome ◽  
Epigallocatechin Gallate ◽  
Host Cells ◽  
Host Responses ◽  
Global Pandemic

Coronavirus Disease 2019 (COVID-19) is a global pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). The rising number of cases of this highly transmissible infection has pressed for the urgent need to find effective therapeutics. The life cycle of SARS-CoV-2 includes the viral entry, viral replication, viral assembly and release. The symptoms associated with viral infection often leads to fatal outcome with pneumonia, myocarditis, acute respiratory distress syndrome, hypercoagulability, and/or multi-organ failure. Recent studies have reported that phytochemicals such as emodin, epigallocatechin gallate, and berberine could, albeit modestly, inhibit different stages of SARS-CoV-2 life cycle. The phytochemicals have been shown to disrupt viral infection and replication by blocking viral-surface spike protein binding to entry receptor angiotensin-converting enzyme (ACE2), inhibiting viral membrane fusion with host cells, inhibiting RNA-dependent RNA polymerase involved in viral replication, and/or pathological host- responses in vitro. The focus of this review is to evaluate the efficacies of these phytochemicals on inhibiting SARS-CoV-2 viral infection, growth, or disease progression as well as to provide a perspective on the potential use of these phytochemicals in the development of novel therapeutics against SARS-CoV-2

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 Silencing Viral MicroRNA as a Novel Antiviral Therapy?

2009 ◽  
Vol 2009 ◽  
pp. 1-18 ◽  
Author(s):  
Ugo Moens
Keyword(s):  
Viral Particle ◽  
Viral Infections ◽  
Host Cells ◽  
Viral Diseases ◽  
Host Immune System ◽  
Intracellular Parasites ◽  
Viral Genes ◽  
Viral Microrna ◽  
Mirnas Expression ◽  
Human Viruses

Viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. Some viruses may also survive by transforming the infected cell into an immortal tumour cell. MicroRNAs are small non-coding transcripts that function as posttranscriptional regulators of gene expression. Viruses encode miRNAs that regulate expression of both cellular and viral genes, and contribute to the pathogenic properties of viruses. Hence, neutralizing the action of viral miRNAs expression by complementary single-stranded oligonucleotides or so-called anti-miRNAs may represent a strategy to combat viral infections and viral-induced pathogenesis. This review describes the miRNAs encoded by human viruses, and discusses the possible therapeutic applications of anti-miRNAs against viral diseases.

scholarly journals TRIM69 Inhibits Vesicular Stomatitis Indiana Virus

2019 ◽  
Vol 93 (20) ◽  
Author(s):  
Suzannah J. Rihn ◽  
Muhamad Afiq Aziz ◽  
Douglas G. Stewart ◽  
Joseph Hughes ◽  
Matthew L. Turnbull ◽  
...  
Keyword(s):  
Viral Replication ◽  
Influenza A ◽  
Viral Infections ◽  
Rift Valley Fever Virus ◽  
Host Cells ◽  
Human Populations ◽  
Valley Fever ◽  
Expression Screening ◽  
Interferon Stimulated Genes ◽  
Vesicular Stomatitis

ABSTRACT Vesicular stomatitis Indiana virus (VSIV), formerly known as vesicular stomatitis virus (VSV) Indiana (VSVIND), is a model virus that is exceptionally sensitive to the inhibitory action of interferons (IFNs). Interferons induce an antiviral state by stimulating the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs can constrain viral replication, limit tissue tropism, reduce pathogenicity, and inhibit viral transmission. Since VSIV is used as a backbone for multiple oncolytic and vaccine strategies, understanding how ISGs restrict VSIV not only helps in understanding VSIV-induced pathogenesis but also helps us evaluate and understand the safety and efficacy of VSIV-based therapies. Thus, there is a need to identify and characterize the ISGs that possess anti-VSIV activity. Using arrayed ISG expression screening, we identified TRIM69 as an ISG that potently inhibits VSIV. This inhibition was highly specific as multiple viruses, including influenza A virus, HIV-1, Rift Valley fever virus, and dengue virus, were unaffected by TRIM69. Indeed, just one amino acid substitution in VSIV can govern sensitivity/resistance to TRIM69. Furthermore, TRIM69 is highly divergent in human populations and exhibits signatures of positive selection that are consistent with this gene playing a key role in antiviral immunity. We propose that TRIM69 is an IFN-induced inhibitor of VSIV and speculate that TRIM69 could be important in limiting VSIV pathogenesis and might influence the specificity and/or efficacy of vesiculovirus-based therapies. IMPORTANCE Vesicular stomatitis Indiana virus (VSIV) is a veterinary pathogen that is also used as a backbone for many oncolytic and vaccine strategies. In natural and therapeutic settings, viral infections like VSIV are sensed by the host, and as a result the host cells make proteins that can protect them from viruses. In the case of VSIV, these antiviral proteins constrain viral replication and protect most healthy tissues from virus infection. In order to understand how VSIV causes disease and how healthy tissues are protected from VSIV-based therapies, it is crucial that we identify the proteins that inhibit VSIV. Here, we show that TRIM69 is an antiviral defense that can potently and specifically block VSIV infection.

scholarly journals The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections

2021 ◽  
Vol 11 ◽  
Author(s):  
Francisco Javier Sánchez-García ◽  
Celia Angélica Pérez-Hernández ◽  
Miguel Rodríguez-Murillo ◽  
María Maximina Bertha Moreno-Altamirano
Keyword(s):  
Viral Replication ◽  
Viral Infections ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Replication Cycle ◽  
Host Cells ◽  
Productive Infection ◽  
The Tca Cycle

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.

scholarly journals The ESCRT-I Subunit Tsg101 Plays Novel Dual Roles in Entry and Replication of Classical Swine Fever Virus

2020 ◽  
pp. JVI.01928-20
Author(s):  
Chun-chun Liu ◽  
Ya-yun Liu ◽  
Yan Cheng ◽  
Yun-Na Zhang ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Classical Swine Fever Virus ◽  
Molecular Mechanisms ◽  
Animal Health ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Host Cells ◽  
Regulatory Role ◽  
High Morbidity ◽  
Replication Process

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is one of the highly contagious diseases of swine with high morbidity and mortality, that negatively affects the pig industry worldwide, in particular China. Soon after the endocytosis of CSFV, the virus makes full use of the components of host cells to complete its life cycle. Endocytosis sorting complex required for transport (ESCRT) system is a central molecular machine for membrane protein sorting and scission in eukaryotic cells that plays an essential role in many physiological, metabolic processes including invasion and egress of envelope viruses. However, the molecular mechanism that ESCRT regulates the replication of CSFV is unknown. In this study, we demonstrated that the ESCRT-I complex Tsg101 protein participates in Clathrin-mediated endocytosis of CSFV and also involved in CSFV trafficking. Tsg101 assisted the virus in entering the host cell through the late endosome (Rab7 and Rab9), and finally to reach the lysosome (Lamp-1). Interestingly, Tsg101 is also involved in the viral replication process by interacting with nonstructural proteins 4B and 5B of CSFV. Finally, confocal microscopy showed that the replication complex of Tsg101 and dsRNA or NS4B and NS5B protein was close to the endoplasmic reticulum (ER), not Golgi in the cytoplasm. Collectively, our finding highlights that Tsg101 regulates the process of CSFV entry and replication, indicating that the ESCRT plays an important role in the life cycle of CSFV. Thus, ESCRT molecules could serve as therapeutic targets to combat CSFV infection.IMPORTANCE CSF, caused by CSFV, is one of the notifiable diseases by the World Organization for Animal Health (OIE) and causes significant financial losses to the pig industry globally. The ESCRT machinery plays an important regulatory role in several members of the genus Flavivirus and Hepacivirus within the family Flaviviridae, such as hepatitis C virus, Japanese encephalitis virus, and dengue virus. Previous reports have shown that assembling and budding of these viruses require ESCRT. However, the role of ESCRT in Pestivirus infection remains to be elucidated. We determined the molecular mechanisms of the regulation of CSFV infection by the major subunit Tsg101 of ESCRT-I. Interestingly, Tsg101 plays an essential regulatory role in both Clathrin-mediated endocytosis and genome replication of CSFV. Overall, the results of this study provide further insights into the molecular function of ESCRT-I complex protein Tsg101 during CSFV infection, which may serve as a molecular target for Pestivirus inhibitors.

scholarly journals Special Issue: “Viral Replication Complexes”

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1902
Author(s):  
Núria Verdaguer ◽  
Diego S. Ferrero
Keyword(s):  
Viral Replication ◽  
Special Issue ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Biological Entities ◽  
Cellular Components

Viruses are extraordinary biological entities that can only thrive as obligate intracellular parasites, exploiting other living cellular components in order to reproduce [...]

scholarly journals Targeting Viral Surface Proteins through Structure-Based Design

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1320
Author(s):  
Yogesh B Narkhede ◽  
Karen J Gonzalez ◽  
Eva-Maria Strauch
Keyword(s):  
Public Health ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Surface Proteins ◽  
Host Cells ◽  
Viral Fusion ◽  
Health It ◽  
Viral Particles ◽  
Pathogenic Viruses ◽  
Viral Surface

The emergence of novel viral infections of zoonotic origin and mutations of existing human pathogenic viruses represent a serious concern for public health. It warrants the establishment of better interventions and protective therapies to combat the virus and prevent its spread. Surface glycoproteins catalyzing the fusion of viral particles and host cells have proven to be an excellent target for antivirals as well as vaccines. This review focuses on recent advances for computational structure-based design of antivirals and vaccines targeting viral fusion machinery to control seasonal and emerging respiratory viruses.

scholarly journals Nucleosome Positioning on Episomal Human Papillomavirus DNA in Cultured Cells

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 772
Author(s):  
Isao Murakami ◽  
Takashi Iwata ◽  
Tohru Morisada ◽  
Kyoko Tanaka ◽  
Daisuke Aoki
Keyword(s):  
Life Cycle ◽  
Cultured Cells ◽  
Basal Layer ◽  
Nucleosome Positioning ◽  
Viral Life Cycle ◽  
Human Papillomaviruses ◽  
Host Cells ◽  
Micrococcal Nuclease ◽  
Hpv Dna ◽  
Dna Replication And Repair

Several human papillomaviruses (HPV) are associated with the development of cervical carcinoma. HPV DNA synthesis is increased during the differentiation of infected host keratinocytes as they migrate from the basal layer of the epithelium to the spinous layer, but the molecular mechanism is unclear. Nucleosome positioning affects various cellular processes such as DNA replication and repair by permitting the access of transcription factors to promoters to initiate transcription. In this study, nucleosome positioning on virus chromatin was investigated in normal immortalized keratinocytes (NIKS) stably transfected with HPV16 or HPV18 genomes to determine if there is an association with the viral life cycle. Micrococcal nuclease-treated DNA analyzed by Southern blotting using probes against HPV16 and HPV18 and quantified by nucleosome scanning analysis using real-time PCR revealed mononucleosomal-sized fragments of 140–200 base pairs that varied in their location within the viral genome according to whether the cells were undergoing proliferation or differentiation. Notably, changes in the regions around nucleotide 110 in proliferating and differentiating host cells were common to HPV16 and HPV18. Our findings suggest that changes in nucleosome positions on viral DNA during host cell differentiation is an important regulatory event in the viral life cycle.

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