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

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.

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Poxviral Strategies to Overcome Host Cell Apoptosis

Pathogens ◽

10.3390/pathogens10010006 ◽

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.

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Role of Mitochondria in Viral Infections

Life ◽

10.3390/life11030232 ◽

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.

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Establishment of Neurospora crassa as a model organism for fungal virology

Nature Communications ◽

10.1038/s41467-020-19355-y ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Shinji Honda ◽

Ana Eusebio-Cope ◽

Shuhei Miyashita ◽

Ayumi Yokoyama ◽

Annisa Aulia ◽

...

Keyword(s):

Viral Replication ◽

Neurospora Crassa ◽

Rna Viruses ◽

Model Organism ◽

Model System ◽

Double Stranded Rna ◽

Antiviral Responses ◽

Positive Sense ◽

Host Virus Interactions ◽

Virus Interactions

Abstract The filamentous fungus Neurospora crassa is used as a model organism for genetics, developmental biology and molecular biology. Remarkably, it is not known to host or to be susceptible to infection with any viruses. Here, we identify diverse RNA viruses in N. crassa and other Neurospora species, and show that N. crassa supports the replication of these viruses as well as some viruses from other fungi. Several encapsidated double-stranded RNA viruses and capsid-less positive-sense single-stranded RNA viruses can be experimentally introduced into N. crassa protoplasts or spheroplasts. This allowed us to examine viral replication and RNAi-mediated antiviral responses in this organism. We show that viral infection upregulates the transcription of RNAi components, and that Dicer proteins (DCL-1, DCL-2) and an Argonaute (QDE-2) participate in suppression of viral replication. Our study thus establishes N. crassa as a model system for the study of host-virus interactions.

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

Pharmaceuticals ◽

10.3390/ph12040147 ◽

2019 ◽

Vol 12 (4) ◽

pp. 147 ◽

Cited By ~ 3

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.

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Unraveling the Underlying Interaction Mechanism Between Dabie bandavirus and Innate Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.676861 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chuan-min Zhou ◽

Xue-jie Yu

Keyword(s):

Interaction Mechanism ◽

Innate Immune ◽

Type I ◽

Innate Immune Responses ◽

Structural Protein ◽

Antiviral Responses ◽

Host Virus Interactions ◽

Virus Interactions ◽

Severe Fever

The genus Bandavirus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. Dabie bandavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.

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

Viruses ◽

10.3390/v12040436 ◽

2020 ◽

Vol 12 (4) ◽

pp. 436 ◽

Cited By ~ 4

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.

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Nudivirus Remnants in the Genomes of Arthropods

Genome Biology and Evolution ◽

10.1093/gbe/evaa074 ◽

2020 ◽

Vol 12 (5) ◽

pp. 578-588 ◽

Cited By ~ 1

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.

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The interplay between viruses and the immune system of bats

Microbiology Australia ◽

10.1071/ma17010 ◽

2017 ◽

Vol 38 (1) ◽

pp. 30

Author(s):

Stacey Leech ◽

Michelle L Baker

Keyword(s):

Immune System ◽

Viral Replication ◽

Viral Infections ◽

Clinical Signs ◽

Innate Immune ◽

Innate Immune Responses ◽

Highly Pathogenic ◽

Vertebrate Hosts ◽

And Migration ◽

Respiratory Coronavirus

Bats are an abundant and diverse group of mammals with an array of unique characteristics, including their well-known roles as natural reservoirs for a variety of viruses. These include the deadly zoonotic paramyxoviruses; Hendra (HeV) and Nipah (NiV)1,2, lyssaviruses3, coronaviruses such as severe acute respiratory coronavirus (SARS-CoV)4 and filoviruses such as Marburg5. Although these viruses are highly pathogenic in other species, including humans, bats rarely show clinical signs of disease whilst maintaining the ability to transmit virus to susceptible vertebrate hosts. In addition, bats are capable of clearing experimental infections with henipaviruses, filoviruses and lyssaviruses at doses of infection that are lethal in other mammals6–12. Curiously, the ability of bats to tolerate viral infections does not appear to extend to extracellular pathogens such as bacteria, fungi and parasites13. Over the past few years, considerable headway has been made into elucidating the mechanisms responsible for the ability of bats to control viral replication, with evidence for unique differences in the innate immune responses of bats14–20. However, many questions remain around mechanisms responsible for the ability of bats to co-exist with viruses, including their ability to tolerate constitutive immune activation, the triggers associated with viral spillover events and the sites of viral replication. Although bats appear to have all of the major components of the immune system present in other species, their unique ecological characteristics (including flight, high density populations and migration) combined with their long co-evolutionary history with viruses has likely shaped their immune response resulting in an equilibrium between the host and its pathogens.

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When human guanylate-binding proteins meet viral infections

Journal of Biomedical Science ◽

10.1186/s12929-021-00716-8 ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Rongzhao Zhang ◽

Zhixin Li ◽

Yan-Dong Tang ◽

Chenhe Su ◽

Chunfu Zheng

Keyword(s):

Innate Immunity ◽

Viral Infection ◽

Binding Proteins ◽

Molecular Mechanisms ◽

Viral Infections ◽

Innate Immune ◽

Type I Interferons ◽

Type I ◽

Downstream Signaling ◽

Antiviral Innate Immunity

AbstractInnate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

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Cytokine storm interference

International Journal of Science and Research Archive ◽

10.30574/ijsra.2021.4.1.0196 ◽

2021 ◽

Vol 4 (1) ◽

pp. 185-187

Author(s):

Michael John Dochniak

Keyword(s):

Innate Immunity ◽

Acute Respiratory Distress Syndrome ◽

Immune System ◽

Innate Immune System ◽

Distress Syndrome ◽

Viral Infections ◽

Acute Infection ◽

Innate Immune ◽

Cytokine Storm ◽

Healthy Individuals

Viral infections are a natural and inevitable part of life. In healthy individuals, mortality increases when the body’s innate immune system quickly activates, creating a cytokine storm. A rapid and excessive release of cytokines into the bloodstream can cause acute respiratory distress syndrome and death. This communication proposes inhibiting cytokine storm development through forced atopy. Hyper-allergenic skin cream therapy stimulates adaptive immunity to support innate immunity before acute infection.

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