scholarly journals Alternative Experimental Models for Studying Influenza Proteins, Host–Virus Interactions and Anti-Influenza Drugs

2019 ◽  
Vol 12 (4) ◽  
pp. 147 ◽  
Author(s):  
Sonja C. J. H. Chua ◽  
Hui Qing Tan ◽  
David Engelberg ◽  
Lina H. K. Lim
Keyword(s):  
Protein Function ◽  
Viral Infections ◽  
Experimental Models ◽  
Host Proteins ◽  
Physiological Basis ◽  
Host Interactions ◽  
Experimental Systems ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Unique Potential

Ninety years after the discovery of the virus causing the influenza disease, this malady remains one of the biggest public health threats to mankind. Currently available drugs and vaccines only partially reduce deaths and hospitalizations. Some of the reasons for this disturbing situation stem from the sophistication of the viral machinery, but another reason is the lack of a complete understanding of the molecular and physiological basis of viral infections and host–pathogen interactions. Even the functions of the influenza proteins, their mechanisms of action and interaction with host proteins have not been fully revealed. These questions have traditionally been studied in mammalian animal models, mainly ferrets and mice (as well as pigs and non-human primates) and in cell lines. Although obviously relevant as models to humans, these experimental systems are very complex and are not conveniently accessible to various genetic, molecular and biochemical approaches. The fact that influenza remains an unsolved problem, in combination with the limitations of the conventional experimental models, motivated increasing attempts to use the power of other models, such as low eukaryotes, including invertebrate, and primary cell cultures. In this review, we summarized the efforts to study influenza in yeast, Drosophila, zebrafish and primary human tissue cultures and the major contributions these studies have made toward a better understanding of the disease. We feel that these models are still under-utilized and we highlight the unique potential each model has for better comprehending virus–host interactions and viral protein function.

scholarly journals Fruits of Virus Discovery: New Pathogens and New Experimental Models

2014 ◽  
Vol 89 (3) ◽  
pp. 1486-1488 ◽  
Author(s):  
David Wang
Keyword(s):  
Infectious Disease ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Experimental Models ◽  
Virus Discovery ◽  
Experimental Systems ◽  
Novel Virus ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Viral Sequences

The advent of high-throughput sequencing has led to a tremendous increase in the rate of discovery of viral sequences. In some instances, novel pathogens have been identified. What has been less well appreciated is that novel virus discoveries in distinct hosts have led to the establishment of unique experimental systems to define host-virus interactions. These new systems have opened new frontiers in the study of fundamental virology and infectious disease.

scholarly journals Poxviral Strategies to Overcome Host Cell Apoptosis

Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Chathura D. Suraweera ◽  
Mark G. Hinds ◽  
Marc Kvansakul
Keyword(s):  
Viral Infections ◽  
B Cell Lymphoma ◽  
Intrinsic Apoptosis ◽  
Host Cell Apoptosis ◽  
Successful Infection ◽  
Infected Cells ◽  
Host Virus Interactions ◽  
Almost All ◽  
Virus Interactions ◽  
Multicellular Organisms

Apoptosis is a form of cellular suicide initiated either via extracellular (extrinsic apoptosis) or intracellular (intrinsic apoptosis) cues. This form of programmed cell death plays a crucial role in development and tissue homeostasis in multicellular organisms and its dysregulation is an underlying cause for many diseases. Intrinsic apoptosis is regulated by members of the evolutionarily conserved B-cell lymphoma-2 (Bcl-2) family, a family that consists of pro- and anti-apoptotic members. Bcl-2 genes have also been assimilated by numerous viruses including pox viruses, in particular the sub-family of chordopoxviridae, a group of viruses known to infect almost all vertebrates. The viral Bcl-2 proteins are virulence factors and aid the evasion of host immune defenses by mimicking the activity of their cellular counterparts. Viral Bcl-2 genes have proved essential for the survival of virus infected cells and structural studies have shown that though they often share very little sequence identity with their cellular counterparts, they have near-identical 3D structures. However, their mechanisms of action are varied. In this review, we examine the structural biology, molecular interactions, and detailed mechanism of action of poxvirus encoded apoptosis inhibitors and how they impact on host–virus interactions to ultimately enable successful infection and propagation of viral infections.

scholarly journals Role of Mitochondria in Viral Infections

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 232
Author(s):  
Srikanth Elesela ◽  
Nicholas W. Lukacs
Keyword(s):  
Viral Infections ◽  
Mitochondrial Dynamics ◽  
The Body ◽  
Viral Diseases ◽  
Multiple Organs ◽  
Innate Immune Signaling ◽  
Mitochondrial Functions ◽  
Host Virus Interactions ◽  
Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

scholarly journals Permissive and restricted virus infection of murine embryonic stem cells

2012 ◽  
Vol 93 (10) ◽  
pp. 2118-2130 ◽  
Author(s):  
Rachael Wash ◽  
Sabrina Calabressi ◽  
Stephanie Franz ◽  
Samantha J. Griffiths ◽  
David Goulding ◽  
...  
Keyword(s):  
Virus Infection ◽  
Embryonic Stem ◽  
Cell Types ◽  
Host Protein ◽  
Host Proteins ◽  
Transformed Cell Lines ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Mes Cells ◽  
Hsv 1

Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA ‘off-target’ effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host–pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host–virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host–virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence.

scholarly journals The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 436 ◽  
Author(s):  
Kavitha Ganesan Nathan ◽  
Sunil K. Lal
Keyword(s):  
Protein Interactions ◽  
Viral Infections ◽  
Pharmaceutical Research ◽  
Host Protein ◽  
Dna Viruses ◽  
Wide Range ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Rna And Dna

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

scholarly journals Nudivirus Remnants in the Genomes of Arthropods

2020 ◽  
Vol 12 (5) ◽  
pp. 578-588 ◽  
Author(s):  
Ruo-Lin Cheng ◽  
Xiao-Feng Li ◽  
Chuan-Xi Zhang
Keyword(s):  
Viral Infections ◽  
Phylogenetic Analyses ◽  
Open Reading Frames ◽  
Endogenous Viral Elements ◽  
Host Virus Interactions ◽  
Fossil Records ◽  
Virus Interactions ◽  
Flanking Regions ◽  
Eukaryotic Genomes ◽  
Reading Frames

Abstract Endogenous viral elements (EVEs), derived from all major types of viruses, have been discovered in many eukaryotic genomes, representing “fossil records” of past viral infections. The endogenization of nudiviruses has been reported in several insects, leading to the question of whether genomic integration is a common phenomenon for these viruses. In this study, genomic assemblies of insects and other arthropods were analyzed to identify endogenous sequences related to Nudiviridae. A total of 359 nudivirus-like genes were identified in 43 species belonging to different groups; however, none of these genes were detected in the known hosts of nudiviruses. A large proportion of the putative EVEs identified in this study encode intact open reading frames or are transcribed as mRNAs, suggesting that they result from recent endogenization of nudiviruses. Phylogenetic analyses of the identified EVEs and inspections of their flanking regions indicated that integration of nudiviruses has occurred recurrently during the evolution of arthropods. This is the first report of a comprehensive screening for nudivirus-derived EVEs in arthropod genomes. The results of this study demonstrated that a large variety of arthropods, especially hemipteran and hymenopteran insects, have previously been or are still infected by nudiviruses. These findings have greatly extended the host range of Nudiviridae and provide new insights into viral diversity, evolution, and host–virus interactions.

scholarly journals Application of CRISPR/Cas9 in Understanding Avian Viruses and Developing Poultry Vaccines

2020 ◽  
Vol 10 ◽  
Author(s):  
Julianne Vilela ◽  
Mohammed A. Rohaim ◽  
Muhammad Munir
Keyword(s):  
Genome Editing ◽  
Genome Instability ◽  
Viral Gene ◽  
Recombinant Vaccines ◽  
Viral Genomes ◽  
Host Interactions ◽  
Avian Diseases ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
User Friendly

Clustered regularly interspaced short palindromic repeats associated protein nuclease 9 (CRISPR-Cas9) technology offers novel approaches to precisely, cost-effectively, and user-friendly edit genomes for a wide array of applications and across multiple disciplines. This methodology can be leveraged to underpin host-virus interactions, elucidate viral gene functions, and to develop recombinant vaccines. The successful utilization of CRISPR/Cas9 in editing viral genomes has paved the way of developing novel and multiplex viral vectored poultry vaccines. Furthermore, CRISPR/Cas9 can be exploited to rectify major limitations of conventional approaches including reversion to virulent form, recombination with field viruses and transgene, and genome instability. This review provides comprehensive analysis of the potential of CRISPR/Cas9 genome editing technique in understanding avian virus-host interactions and developing novel poultry vaccines. Finally, we discuss the simplest and practical aspects of genome editing approaches in generating multivalent recombinant poultry vaccines that conform simultaneous protection against major avian diseases.

scholarly journals To TRIM or not to TRIM: the balance of host–virus interactions mediated by the ubiquitin system

2019 ◽  
Vol 100 (12) ◽  
pp. 1641-1662 ◽  
Author(s):  
Adam Hage ◽  
Ricardo Rajsbaum
Keyword(s):  
Innate Immunity ◽  
Viral Replication ◽  
Viral Infections ◽  
Ubiquitin Ligases ◽  
Innate Immune ◽  
Future Research ◽  
Post Translational Modifications ◽  
Ubiquitin System ◽  
Host Virus Interactions ◽  
Virus Interactions

The innate immune system responds rapidly to protect against viral infections, but an overactive response can cause harmful damage. To avoid this, the response is tightly regulated by post-translational modifications (PTMs). The ubiquitin system represents a powerful PTM machinery that allows for the reversible linkage of ubiquitin to activate and deactivate a target’s function. A precise enzymatic cascade of ubiquitin-activating, conjugating and ligating enzymes facilitates ubiquitination. Viruses have evolved to take advantage of the ubiquitin pathway either by targeting factors to dampen the antiviral response or by hijacking the system to enhance their replication. The tripartite motif (TRIM) family of E3 ubiquitin ligases has garnered attention as a major contributor to innate immunity. Many TRIM family members limit viruses either indirectly as components in innate immune signalling, or directly by targeting viral proteins for degradation. In spite of this, TRIMs and other ubiquitin ligases can be appropriated by viruses and repurposed as valuable tools in viral replication. This duality of function suggests a new frontier of research for TRIMs and raises new challenges for discerning the subtleties of these pro-viral mechanisms. Here, we review current findings regarding the involvement of TRIMs in host–virus interactions. We examine ongoing developments in the field, including novel roles for unanchored ubiquitin in innate immunity, the direct involvement of ubiquitin ligases in promoting viral replication, recent controversies on the role of ubiquitin and TRIM25 in activation of the pattern recognition receptor RIG-I, and we discuss the implications these studies have on future research directions.

scholarly journals Experimental Microbiomes: Models Not to Scale

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Marc G. Chevrette ◽  
Jennifer R. Bratburd ◽  
Cameron R. Currie ◽  
Reed M. Stubbendieck
Keyword(s):  
Molecular Mechanisms ◽  
Low Cost ◽  
Experimental Models ◽  
Microbial Composition ◽  
Content Type ◽  
New Era ◽  
Practical Applications ◽  
Host Interactions ◽  
Experimental Systems ◽  
Gnotobiotic Mice

ABSTRACT Low-cost, high-throughput nucleic acid sequencing ushered the field of microbial ecology into a new era in which the microbial composition of nearly every conceivable environment on the planet is under examination. However, static “screenshots” derived from sequence-only approaches belie the underlying complexity of the microbe-microbe and microbe-host interactions occurring within these systems. Reductionist experimental models are essential to identify the microbes involved in interactions and to characterize the molecular mechanisms that manifest as complex host and environmental phenomena. Herein, we focus on three models (Bacillus-Streptomyces, Aliivibrio fischeri-Hawaiian bobtail squid, and gnotobiotic mice) at various levels of taxonomic complexity and experimental control used to gain molecular insight into microbe-mediated interactions. We argue that when studying microbial communities, it is crucial to consider the scope of questions that experimental systems are suited to address, especially for researchers beginning new projects. Therefore, we highlight practical applications, limitations, and tradeoffs inherent to each model.

vhfRNAi: a web-platform for analysis of host genes involved in viral infections discovered by genome wide RNAi screens

2017 ◽  
Vol 13 (7) ◽  
pp. 1377-1387 ◽  
Author(s):  
Anamika Thakur ◽  
Abid Qureshi ◽  
Manoj Kumar
Keyword(s):  
Rna Interference ◽  
High Throughput ◽  
Viral Infections ◽  
Host Factors ◽  
Genome Wide ◽  
Host Virus Interactions ◽  
Virus Interactions ◽  
Web Platform ◽  
Host Genes

Knockdown of host genes using high-throughput genome-wide RNA interference screens has identified numerous host factors that affect viral infections, which would be helpful in understanding host–virus interactions.

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