scholarly journals Viral transduction and the dynamics of bacterial adaptation

2021 ◽  
Author(s):  
Philippe Cherabier ◽  
Sylvie Meleard ◽  
Regis Ferriere
Keyword(s):  
Viral Infections ◽  
Phenotypic Diversity ◽  
Genetic Material ◽  
Evolutionary Model ◽  
Host Cells ◽  
Major Pathway ◽  
Bacterial Adaptation ◽  
Deleterious Alleles ◽  
Stochastic Fluctuations ◽  
Viral Transduction

Viral infections can exert a large influence on their hosts' ecology by causing widespread mortality, but they also shape the evolutionary adaptation of hosts in a number of ways. A major pathway for viruses to do so is through the transfer of genetic material among individual hosts, a process known as transduction. While horizontal gene transfer is known as a major factor in prokaryotic macroevolution, its role in the microevolutionary adaptation of hosts populations is poorly known. By facilitating the transfer of beneficial alleles between host cells, transduction might facilitate and accelerate bacterial adaptation. Conversely, the risk of transferring deleterious alleles may hinder and slow it down. Here we resolve the effect of transduction on bacterial adaptation in a simple eco-evolutionary model for the combined dynamics of transduction and adaptive evolution of an ecological (resource-use) trait. The transfer of beneficial alleles by tranduction speeds up adaptation whereas the transfer of deleterious alleles causes strong stochastic fluctuations of the trait value around the adapted value. In contrast to the expected effect of recombination, which tends to oppose phenotypic diversification, viral transduction can increase host phenotypic diversity.

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 The Interferon-Stimulated Gene IFITM3 Restricts Infection and Pathogenesis of Arthritogenic and Encephalitic Alphaviruses

2016 ◽  
Vol 90 (19) ◽  
pp. 8780-8794 ◽  
Author(s):  
Subhajit Poddar ◽  
Jennifer L. Hyde ◽  
Matthew J. Gorman ◽  
Michael Farzan ◽  
Michael S. Diamond
Keyword(s):  
Viral Infections ◽  
Transmembrane Protein ◽  
Flow Cytometric Analysis ◽  
Antiviral Effect ◽  
Host Cells ◽  
Type I ◽  
Targeted Gene Deletion ◽  
Multiple Organs ◽  
Viral Burden ◽  
Alphavirus Infection

ABSTRACTHost cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased inIfitm3−/−andIfitmlocus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis,Ifitm3−/−mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested thatIfitm3−/−macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments withIfitm3−/−bone marrow-derived macrophages.Ifitm3−/−mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.IMPORTANCEThe interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion ofIfitm3as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

scholarly journals Reovirus core proteins λ1 and σ2 promote stability of disassembly intermediates and influence early replication events

2020 ◽  
Author(s):  
Stephanie Gummersheimer ◽  
Pranav Danthi
Keyword(s):  
Conformational Changes ◽  
Genetic Material ◽  
Point Mutations ◽  
Host Cells ◽  
Capsid Proteins ◽  
Endosomal Membrane ◽  
The Core ◽  
Core Proteins ◽  
Early Replication ◽  
Outer Capsid

ABSTRACTThe capsids of mammalian reovirus contain two concentric protein shells, the core and the outer capsid. The outer capsid is comprised of µ1-σ3 heterohexamers which surround the core. The core is comprised of λ1 decamers held in place by σ2. After entry into the endosome, σ3 is proteolytically degraded and µ1 is cleaved and exposed to form ISVPs. ISVPs undergo further conformational changes to form ISVP*s, resulting in the release of µ1 peptides which facilitate the penetration of the endosomal membrane to release transcriptionally active core particles into the cytoplasm. Previous work has identified regions or specific residues within reovirus outer capsid that impact the efficiency of cell entry. We examined the functions of the core proteins λ1 and σ2. We generated a reovirus T3D reassortant that carries strain T1L derived σ2 and λ1 proteins (T3D/T1L L3S2). This virus displays a lower ISVP stability and therefore converts to ISVP*s more readily. To identify the basis for lability of T3D/T1L L3S2, we screened for hyper-stable mutants of T3D/T1L L3S2 and identified three point mutations in µ1 that stabilize ISVPs. Two of these mutations are located in the C-terminal ϕ region of µ1, which has not previously been implicated in controlling ISVP stability. Independent from compromised ISVP stability, we also found that T3D/T1L L3S2 launches replication more efficiently and produces higher yields in infected cells. In addition to identifying a new role for the core proteins in disassembly events, these data highlight that core proteins may influence multiple stages of infection.IMPORTANCEProtein shells of viruses (capsids) have evolved to undergo specific changes to ensure the timely delivery of genetic material to host cells. The 2-layer capsid of reovirus provides a model system to study the interactions between capsid proteins and the changes they undergo during entry. We tested a virus in which the core proteins were derived from a different strain than the outer capsid. We found that this mismatched virus was less stable and completed conformational changes required for entry prematurely. Capsid stability was restored by introduction of specific changes to the outer capsid, indicating that an optimal fit between inner and outer shells maintains capsid function. Separate from this property, mismatch between these protein layers also impacted the capacity of virus to initiate infection and produce progeny. This study reveals new insights into the roles of capsid proteins and their multiple functions during viral replication.

scholarly journals Trasposon Mediated Horizontal Gene Transfer (T-HGT) of Circulating Tumor DNA Reshapes MM Clonal Architecture

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3065-3065
Author(s):  
Munevver Cinar ◽  
Steven Flygare ◽  
Marina Mosunjac ◽  
Ganji Nagaraju ◽  
Dongkyoo Park ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Drug Sensitivity ◽  
Genetic Material ◽  
Host Cells ◽  
Response To Treatment ◽  
Hierarchical Architecture ◽  
Tumor Evolution ◽  
Sequencing Analysis

Spatial genetic heterogeneity is a characteristic phenomenon that influences multiple myeloma's (MM) phenotype and drug sensitivity (Rasche L. et al and Bolli N et al.). Hence, the branch model of tumor evolution is not sufficient to explain the disorganized architecture observed in MM. In this study, we investigated whether MM ctDNA horizontal gene transfer (HGT) affect tumor genetic architecture and drug sensitivity, resembling what is seen in prokaryotes, and elucidated the mechanisms involved in the mobilization of genetic material from one cell to another. We identified that plasma from patients with MM transmits drug sensitivity or resistance to cells in culture. This transmission of drug sensitivity is mediated by ctDNA transfer of oncogenes to a host cell. Importantly, in vitro and in vivo demonstrated that ctDNA mainly targets cells resembling the cell of origin (tropism). Karyotype spreads and whole genome sequencing demonstrated that once patients ctDNA encounters host cells, it migrates into the nucleus where it ultimately integrates into the cell's genome. Integration to the genome was confirmed to be targeted to myeloma cells. Further sequencing analysis of multiple MM samples identified ctDNA tropism and integration is dependent on the 5' and 3' end presence of transposable elements (TE), particularly of the MIR and ALUsq family. These results were further validated by TE mediated delivery of GFP into MM cells in vitro and HSVTK in tumors of mouse xenografts. In conclusion, this data indicates for the first time that TE mediates MM ctDNA HGT into homologous tumor cells shaping the hierarchical architecture of tumor clones and affecting tumor response to treatment. Therapeutically, this unique quality of ctDNA can be exploited for targeted gene therapeutic approaches in MM and potentially other cancers. Disclosures Bernal-Mizrachi: Kodikas Therapeutic Solutions, Inc: Equity Ownership; TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents & Royalties.

scholarly journals Silver Nanoparticles as Potential Antiviral Agents

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2034
Author(s):  
Zubair Ahmed Ratan ◽  
Fazla Rabbi Mashrur ◽  
Anisha Parsub Chhoan ◽  
Sadi Md. Shahriar ◽  
Mohammad Faisal Haidere ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Potential Role ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Host Cells ◽  
Characterization Methods ◽  
New Horizons ◽  
Bacteria And Fungi ◽  
The Impact

Since the early 1990s, nanotechnology has led to new horizons in nanomedicine, which encompasses all spheres of science including chemistry, material science, biology, and biotechnology. Emerging viral infections are creating severe hazards to public health worldwide, recently, COVID-19 has caused mass human casualties with significant economic impacts. Interestingly, silver nanoparticles (AgNPs) exhibited the potential to destroy viruses, bacteria, and fungi using various methods. However, developing safe and effective antiviral drugs is challenging, as viruses use host cells for replication. Designing drugs that do not harm host cells while targeting viruses is complicated. In recent years, the impact of AgNPs on viruses has been evaluated. Here, we discuss the potential role of silver nanoparticles as antiviral agents. In this review, we focus on the properties of AgNPs such as their characterization methods, antiviral activity, mechanisms, applications, and toxicity.

scholarly journals Genome-Wide Analysis Reveals Genetic Structure and Selective Sweeps in Chinese Indigenous Pig Breeds

2019 ◽  
Author(s):  
Xiong Tong ◽  
Lianjie Hou ◽  
Weiming He ◽  
Chugang Mei ◽  
Bo Huang ◽  
...  
Keyword(s):  
Yangtze River ◽  
North China ◽  
Phenotypic Diversity ◽  
Southern China ◽  
Linkage Disequilibrium Block ◽  
Genetic Material ◽  
Morphological Characteristics ◽  
Central China ◽  
Pig Breeds ◽  
Southern Chinese

Abstract Background Chinese indigenous pigs exhibit considerable phenotypic diversity, but their population structure and the genetic basis of agriculturally important traits have not been explored. Results Here, we sequenced the whole genomes of 24 individual pigs representing 22 breeds distributed throughout China. For comparison with European and commercial breeds (one pig per breed), we integrated seven published pig genomes with our new genomes. Our results showed that pig domestication occurred at three places in Southeastern Asia, namely the Mekong region, the middle to downstream regions of the Yangtze River, and Tibetan highlands. Moreover, we demonstrated that classic morphological characteristics such as coat color are not consistent with genetic data. We found that genetic material from European pigs likely introgressed into five Chinese breeds. Two new subpopulations of domestic pigs have been identified in South and North China that encompass morphology-based criteria. The Southern Chinese subpopulation comprises the classical Southern China Type and part of the Central China Type, whereas the Northern Chinese subpopulation comprises the North China Type, the Lower Yangtze River Basin Type, the Southwest Type, the Plateau Type, and the remainder of the Central China Type. Eight haplotypes and two recombination sites were identified within a conserved 40.09 Mb linkage-disequilibrium block on the X chromosome. Potential selection and domestication signatures were identified, mainly influencing body size, along with adaptations to cold and hot temperature environments. Conclusions Our findings provide insights into the phylogeny of Chinese indigenous pig breeds, and will be of enormous benefit in identifying beneficial genes to develop superior pig breeds.

scholarly journals Molecular mechanisms of human herpes viruses inferring with host immune surveillance

2020 ◽  
Vol 8 (2) ◽  
pp. e000841
Author(s):  
Simon Jasinski-Bergner ◽  
Ofer Mandelboim ◽  
Barbara Seliger
Keyword(s):  
Immune Evasion ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Immune Surveillance ◽  
Host Cells ◽  
Herpes Viruses ◽  
Molecular Processes ◽  
Human Herpes ◽  
Human Herpes Viruses

Several human herpes viruses (HHVs) exert oncogenic potential leading to malignant transformation of infected cells and/or tissues. The molecular processes induced by viral-encoded molecules including microRNAs, peptides, and proteins contributing to immune evasion of the infected host cells are equal to the molecular processes of immune evasion mediated by tumor cells independently of viral infections. Such major immune evasion strategies include (1) the downregulation of proinflammatory cytokines/chemokines as well as the induction of anti-inflammatory cytokines/chemokines, (2) the downregulation of major histocompatibility complex (MHC) class Ia directly as well as indirectly by downregulation of the components involved in the antigen processing, and (3) the downregulation of stress-induced ligands for activating receptors on immune effector cells with NKG2D leading the way. Furthermore, (4) immune modulatory molecules like MHC class Ib molecules and programmed cell death1 ligand 1 can be upregulated on infections with certain herpes viruses. This review article focuses on the known molecular mechanisms of HHVs modulating the above-mentioned possibilities for immune surveillance and even postulates a temporal order linking regular tumor immunology with basic virology and offering putatively novel insights for targeting HHVs.

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.

scholarly journals Antiviral Activity of a Turbot (Scophthalmus maximus) NK-Lysin Peptide by Inhibition of Low-pH Virus-Induced Membrane Fusion

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 87 ◽  
Author(s):  
Alberto Falco ◽  
Regla Medina-Gali ◽  
José Poveda ◽  
Melissa Bello-Perez ◽  
Beatriz Novoa ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Scophthalmus Maximus ◽  
Low Ph ◽  
Host Cells ◽  
Viral Origin ◽  
Membrane Rupture ◽  
Viral Particles ◽  
Strong Antiviral Activity ◽  
Turbot Scophthalmus Maximus

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl71–100 is shown as a promising broad-spectrum antiviral candidate.

scholarly journals Antiviral Potential of Nanoparticles—Can Nanoparticles Fight Against Coronaviruses?

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1645 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Muhammad Qasim ◽  
Youngsok Choi ◽  
Jeong Tae Do ◽  
Chankyu Park ◽  
...  
Keyword(s):  
Global Economy ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Host Cells ◽  
Economic Losses ◽  
Therapeutic Approaches ◽  
Organic Nanoparticles ◽  
Antiviral Therapies ◽  
Low Probability

Infectious diseases account for more than 20% of global mortality and viruses are responsible for about one-third of these deaths. Highly infectious viral diseases such as severe acute respiratory (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease (COVID-19) are emerging more frequently and their worldwide spread poses a serious threat to human health and the global economy. The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of 27 July 2020, SARS-CoV-2 has infected over 16 million people and led to the death of more than 652,434 individuals as on 27 July 2020 while also causing significant economic losses. To date, there are no vaccines or specific antiviral drugs to prevent or treat COVID-19. Hence, it is necessary to accelerate the development of antiviral drugs and vaccines to help mitigate this pandemic. Non-Conventional antiviral agents must also be considered and exploited. In this regard, nanoparticles can be used as antiviral agents for the treatment of various viral infections. The use of nanoparticles provides an interesting opportunity for the development of novel antiviral therapies with a low probability of developing drug resistance compared to conventional chemical-based antiviral therapies. In this review, we first discuss viral mechanisms of entry into host cells and then we detail the major and important types of nanomaterials that could be used as antiviral agents. These nanomaterials include silver, gold, quantum dots, organic nanoparticles, liposomes, dendrimers and polymers. Further, we consider antiviral mechanisms, the effects of nanoparticles on coronaviruses and therapeutic approaches of nanoparticles. Finally, we provide our perspective on the future of nanoparticles in the fight against viral infections.

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