Cellular Host Defense Research Articles

PoIL8-L, a teleost interleukin-8 like, enhances leukocyte cellular vitality and host defense against bacterial infections in Japanese flounder (Paralichthys olivaceus)

Interleukin-8 (IL-8), a CXC chemokine, exerts pivotal effect on cell migration, inflammatory response, and immune regulation. In this study, we examined the immunological characteristics of an IL-8 like homologue (PoIL8-L) in Japanese flounder (Paralichthys olivaceus). PoIL8-L contains a conserved chemokine CXC domain and 105 amino acid residues. PoIL8-L expression in tissues was constitutive, and significantly regulated by V. havieri or E. tarda infection. In vitro, rPoIL8-L could bind to eight tested bacteria, exhibited bacteriostatic and bactericidal effects against certain bacteria, and could bind to the targeted bacterial Ⅳ pilin protein rPilA of E. tarda. Furthermore, rPoIL8-L could attach to peripheral blood leukocytes, and enhance their immune genes expression, respiratory burst, chemotaxis, proliferation, acid phosphatase activity, and phagocytic activity. Additionally, rPoIL8-L induce neutrophils to extrude neutrophil extracellular traps. In vivo, rPoIL8-L could promote host resistance to E. tarda infection. In summary, these findings provide fresh perspectives on the immunological antibacterial properties of IL-8 in teleost.

The RXLR effector PpE18 of Phytophthora parasitica is a virulence factor and suppresses peroxisome membrane-associated ascorbate peroxidase NbAPX3-1-mediated plant immunity.

Phytophthora parasitica causes diseases on a broad range of host plants. It secretes numerous effectors to suppress plant immunity. However, only a few virulence effectors in P. parasitica have been characterized. Here, we highlight that PpE18, a conserved RXLR effector in P. parasitica, was a virulence factor and suppresses Nicotiana benthamiana immunity. Utilizing luciferase complementation, co-immunoprecipitation, and GST pull-down assays, we determined that PpE18 targeted NbAPX3-1, a peroxisome membrane-associated ascorbate peroxidase with reactive oxygen species (ROS)-scavenging activity and positively regulates plant immunity in N. benthamiana. We show that the ROS-scavenging activity of NbAPX3-1 was critical for its immune function and was hindered by the binding of PpE18. The interaction between PpE18 and NbAPX3-1 resulted in an elevation of ROS levels in the peroxisome. Moreover, we discovered that the ankyrin repeat-containing protein NbANKr2 acted as a positive immune regulator, interacting with both NbAPX3-1 and PpE18. NbANKr2 was required for NbAPX3-1-mediated disease resistance. PpE18 competitively interfered with the interaction between NbAPX3-1 and NbANKr2, thereby weakening plant resistance. Our results reveal an effective counter-defense mechanism by which P. parasitica employed effector PpE18 to suppress host cellular defense, by suppressing biochemical activity and disturbing immune function of NbAPX3-1 during infection.

Effects of Antimicrobial Peptides on Antioxidant Properties, Non-specific Immune Response and Gut Microbes of Tsinling Lenok Trout (Brachymystax lenok tsinlingensis).

Antimicrobial peptides (AMPs) are an important part of non-specific immunity and play a key role in the cellular host defense against pathogens and tissue injury infections. We investigated the effects of AMP supplementation on the antioxidant capacity, non-specific immunity, and gut microbiota of tsinling lenok trout. 240 fish were fed diets (CT, A120, A240 and A480) containing different amounts of AMP peptides (0, 120mgkg-1, 240mgkg-1, 480mgkg-1) for 8weeks. Our results showed that the activity of total antioxidant capacity (T-SOD) and glutathione peroxidase (GSH-Px), lysozyme (LZM), catalase (CAT) and acid phosphatase (ACP) in the A240 and A480 group were higher than that in the CT group (P < 0.05). The content of malondialdehyde (MDA) in AMP group was significantly lower than that in CT group (P < 0.05). Furthermore, we harvested the mid-gut and applied next-generation sequencing of 16S rDNA. The results showed that the abundance of Halomonas in AMP group was significantly lower than that in CT group. Functional analysis showed that the abundance of chloroalkane and chloroalkene degradation pathway increased significantly in AMP group. In conclusion, AMP enhanced the antioxidant capacity, non-specific immunity, and intestinal health of tsinling lenok trout.

Signaling Pathway Governed by Lipid Derived Molecules as Secondary Messenger

Research shown that the cell death, particularly apoptosis, can extend beyond single cell boundaries. Gap junctions IP3 diffusion, and sphingolipids play significant roles in membrane biology and regulation of cell function. S1P plays crucial role in the cardiovascular and immune systems, serving as a mediator of signaling during cell migration, differentiation, proliferation, and apoptosis. Intestinal phospholipid metabolism, including 1B phospholipase A2 and autotaxin-mediated pathways, contributes to cardiometabolic diseases through multiple mechanisms. A potential strategy for treating cardiovascular and metabolic diseases is the therapeutic suppression of1B phospholipase A2 and autotaxin in the gastrointestinal tract. Cellular stress signalling, inflammation, resolution, and host defence responses are all significantly influenced by lysophospholipids such LPA and S1P. New therapies for cancer, vascular diseases, fibrotic disorders, and autoimmune diseases have been made possible by developments in lysophospholipid research.

Human inborn errors of immunity associated with IRF4.

The transcription factor interferon regulatory factor 4 (IRF4) belongs to the IRF family and has several important functions for the adaptive immune response. Mutations affecting IRF family members IRF1, IRF3, IRF7, IRF8, or IRF9 have been described in patients presenting with inborn errors of immunity (IEI) highlighting the importance of these factors for the cellular host defense against mycobacterial and/or viral infections. IRF4 deficiency and haploinsufficiency have been associated with IEI. More recently, two novel IRF4 disease-causing mechanisms have been described due to the characterization of IEI patients presenting with cellular immunodeficiency associated with agammaglobulinemia. Here, we review the phenotypes and physiopathological mechanisms underlying IEI of IRF family members and, in particular, IRF4.

MicroRNA sequencing analysis reveals injury-induced immune responses of Scylla paramamosain against cheliped autotomy

During pond culture or intensive culture system of crabs (mainly Eriocheir sinensis, Portunus trituberculatus and Scylla paramamosain), high-density farming has typically contributed to a higher limb autotomy level in juvenile animals, especially in S. paramamosain which has a high level of cannibalism. Due to the high limb autotomy level, the survival and growth rates in S. paramamosain farming are restricted, which limit the growth of the mud crab farming industry. MicroRNAs (miRNAs) are small noncoding RNAs that regulate a series of biological processes including innate immune responses by post-transcriptional suppression of their target genes. MiRNAs are believed to be crucial for innate immune process of host wound healing. Many miRNAs have been verified to be required in host immune responses to repair wound and to defense pathogen after tissue damage. However, to our best knowledge, the miRNAs functions of crustacean innate immune reactions against injury induced by limb autotomy have not been studied yet. Here in this study, for the first time, miRNAs involved in the S. paramamosain immune reactions against injury induced by cheliped autotomy were obtained by high-throughput sequencing. A total of 575 miRNAs (518 known miRNAs and 57 novel predicted miRNAs) were obtained, of which 141 differentially expressed microRNAs (93 up-regulated microRNAs and 48 down-regulated microRNAs) were revealed to be modified against cheliped autotomy, and the qPCR results of randomly selected miRNAs confirmed the expression patterns in the miRNAs sequencing data. Numerous immune-related target genes associated with innate immune system were mediated by miRNAs to induce host humoral immune and cellular immune defense to minimize acute physical damage. Furthermore, the genes expression in hemolymph coagulation and melanization pathways, as well as Toll and Imd signaling pathways were mediated by miRNAs to activate host immune responses including melanization and antimicrobial peptides for rapid wound healing and killing invaded pathogens. These results will help to understand injury-induced immune responses in crabs and to develop an effective control strategy of autotomy rate in crabs farming.

Cotton leaf curl Multan virus C4 protein suppresses autophagy to facilitate viral infection.

Autophagy plays an important role in plant antiviral defense. Several plant viruses are reported to encode viral suppressor of autophagy (VSA) to prevent autophagy for effective virus infection. However, whether and how other viruses, in particular DNA viruses, also encode VSAs to affect viral infection in plants is unknown. Here, we report that the C4 protein encoded by Cotton leaf curl Multan geminivirus (CLCuMuV) inhibits autophagy by binding to the autophagy negative regulator eukaryotic translation initiation factor 4A (eIF4A) to enhance the eIF4A-Autophagy-related protein 5 (ATG5) interaction. By contrast, the R54A or R54K mutation in C4 abolishes its capacity to interact with eIF4A, and neither C4R54A nor C4R54K can suppress autophagy. However, the R54 residue is not essential for C4 to interfere with transcriptional gene silencing or post-transcriptional gene silencing. Moreover, plants infected with mutated CLCuMuV-C4R54K develop less severe symptoms with decreased levels of viral DNA. These findings reveal a molecular mechanism underlying how the DNA virus CLCuMuV deploys a VSA to subdue host cellular antiviral autophagy defense and uphold viral infection in plants.

492 Phagocyte heterogeneity and T cell dependence of cellular host defense mechanisms in tuberculosis

OBJECTIVES/GOALS: Phagocytes, diverse cells that ingest material, are the primary cell type infected by Mycobacterium tuberculosis (Mtb) and the executors of protective mechanisms. T cells play a critical role by helping phagocytes control the infection. Understanding the precise T cell-dependent mechanisms by which phagocytic cell types contain Mtb is critical. METHODS/STUDY POPULATION: To determine the impact T cells have on different phagocyte cell populations’ host defense mechanisms, groups of wild–type and T cell deficient TCRa-/- mice were infected with an Mtb strain expressing fluorescent mScarlet protein. At four weeks post-infection, a time when T cell help contributes to control of Mtb, lungs were homogenized and cells sorted based on detection of mScarlet, indicating Mtb-infected cells. Cell suspensions from each mouse background were underwent single-cell RNA sequencing analysis to reveal the heterogenous cellular transcriptional response of different phagocyte populations. RESULTS/ANTICIPATED RESULTS: We found that Mtb-infected phagocytes from wild-type and TCRa-/- mouse lungs contain the same dominant cell phenotypic clusters, but these have different patterns of gene expression. Without T cells, phagocytes are prone to a more inflammatory phenotype. DISCUSSION/SIGNIFICANCE: This will translate fundamental biological data to test the hypothesis that Mtb encounters different environmental stresses exerted by different phagocytic cell types. This work could reveal host intracellular niches that enable bacterial persistence and elucidate new pathways that could be targeted for traditional antibiotic therapies for TB.

Myxozoan fish diseases: possible treatment and zoonoses.

Myxozoan parasites pose huge threat to wild and cultured fishes and reported to cause heavy mortality, retarded growth and post-harvest quality degradation. It is one of the highly divergent groups of parasites which infects skin, gill, muscle, cartilage and internal organs of host fish and the severity of pathology varies depending on the water temperature, species of fish, site of tissue infection and immune resistance of the individual host. Most infections are difficult to treat, as they can easily evade host cellular and humoral defence mechanisms by proliferating or migrating through immune compromised sites of the host and forming large plasmodia encapsulated by the host cellular elements. This spore-forming parasite is harmless to humans but often detected in faecal samples of immunosuppressed humans. The incidences are mostly associated with the consumption of infected fish having a high concentration of spores which causes diarrhea and stomach pain. Currently, there are no immunostimulants or vaccines available for controlling these parasites, however, fumagillin is the drug of choice in fish for controlling this parasitic infection. Excessive usage of fumagillin causes tissue damage and retarded growth in fish, hence feed incorporation of this antibiotic in proper dose is essential for effective treatment. In this review detailed information on the diseases caused by myxozoan parasites in fishes and their zoonotic potential is discussed.

RGD-Labeled Hemocytes With High Migration Activity Display a Potential Immunomodulatory Role in the Pacific Oyster Crassostrea gigas.

Immunocyte migration to infection sites is important for host cellular defense, but the main types of migrating hemocytes and their mechanisms against pathogen invasions are unclear in invertebrates. In the present study, a population of hemocytes in the Pacific oyster Crassostrea gigas labeled with a fluorescein isothiocyanate (FITC)-conjugated Arg-Gly-Asp (RGD)-containing peptide was sorted. RGD+ hemocytes were characterized by a smaller cell size and cytoplasmic-nucleo ratio, fewer cytoplasmic granules, and higher levels of myeloperoxidase, reactive oxygen species, and intracellular free calcium concentration. RGD+ hemocytes exhibited a high level of migration activity, which was further induced after V. splendidus infection. Transcriptome analysis revealed that RGD+ hemocytes highly expressed a series of migration-related genes, which together with migration-promoting genes were significantly upregulated after V. splendidus infection. The neuroendocrine system was also proven to regulate the migration activity of RGD+ hemocytes, especially with the excitatory neuroendocrine factor dopamine, which promoted migration activity as confirmed by receptor blocking assays. Meanwhile, RGD+ hemocytes could highly express immunomodulatory factor interleukin (IL)-17s and their receptor genes, which was positively related to the production of antimicrobial peptides in whole hemocytes after V. splendidus infection. Collectively, this study identified a specific hemocyte population, i.e., RGD+ hemocytes, that shows high migration activity in response to pathogen infection and exerts a potential immunomodulatory role by highly expressing IL-17s that might enhance the hemocytes’ antimicrobial peptide production in oysters.

Analysis of Differentially Expressed Rice Genes Reveals the ATP-Binding Cassette Transporters as Candidate Genes Against the Sheath Blight Pathogen, Rhizoctonia solani

Sheath blight is a serious rice disease worldwide, and genes involved in resistance remain unclear. In the present study, a virulent field isolate of Rhizoctonia solani was used to inoculate detached leaves of a sheath blight-resistant rice cultivar, Jasmine 85; a suppression subtractive cDNA library was constructed using RNA isolated 16 h postinoculation (hpi); and differentially expressed genes were identified from the cDNA library. A total of 159 uniquely expressed sequence tags were identified, including 105 from rice with enrichment in categories related to cellular response, molecular signaling, and host defense. Coupled with gene expression studies by DNA microarray, 27 highly induced genes involved in signal transduction and defense responses were identified within 16 hpi. Three members of the ATP-binding cassette (ABC) transporter gene family ( OsABC1, OsABC9, and OsABC12) encoding pleiotropic drug resistance-like ABC transporters were mapped to different sheath blight resistance quantitative trait loci (QTLs), and their differential expressions were validated. Three high-resolution melting (HRM) markers were developed from these ABC gene family members to distinguish alleles between sheath blight-susceptible cultivar Lemont and resistant cultivar Jasmine 85. Association of sheath blight resistance to these HRM markers was examined in 77 recombinant inbred lines derived from the cross between Jasmine 85 and Lemont. The OsABC9 gene located in a major sheath blight resistance QTL qShB9-2 showed a major contribution to sheath blight resistance. These results are useful for marker-assisted selection and functional validation of the ABC genes in sheath blight disease resistance. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

Autophagic checks and balances of cellular immune responses.

IRF3 (interferon regulatory factor 3) is a critical component of the antiviral innate immune response. IRF3 deficiency causes detrimental effects to the host during virus infection. Dysregulation of IRF3 functions is associated with viral, inflammatory, and hepatic diseases. Both transcriptional and pro-apoptotic activities of IRF3 are involved in the exacerbated inflammation and apoptosis in liver injury induced by ethanol and high-fat diets. Therefore, regulation of IRF3 activities has consequences, and it is a potential therapeutic target for infectious and inflammatory diseases. We recently revealed that IRF3 is degraded by a small molecule, auranofin, by activating the cellular macroautophagy/autophagy pathway. Autophagy is a catabolic pathway that contributes to cellular homeostasis and antiviral host defense. Degradation of IRF3 by autophagy may be a novel strategy used by the viruses to their benefit. In addition, IRF3 functions are harmful in other diseases, including liver injury and bacterial infection. A better understanding of the role of autophagy in regulating IRF3 functions has significant implications in developing therapeutic strategies. Therefore, autophagy provides checks and balances in the innate immune response.

Lysophospholipid Mediators in Health and Disease.

Lysophospholipids, exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are produced by the metabolism and perturbation of biological membranes. Both molecules are established extracellular lipid mediators that signal via specific G protein-coupled receptors in vertebrates. This widespread signaling axis regulates the development, physiological functions, and pathological processes of all organ systems. Indeed, recent research into LPA and S1P has revealed their important roles in cellular stress signaling, inflammation, resolution, and host defense responses. In this review, we focus on how LPA regulates fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and disorders of neuroectodermal development such as hydrocephalus and alopecia. In addition, we discuss how S1P controls collective behavior, apoptotic cell clearance, and immunosurveillance of cancers. Advances in lysophospholipid research have led to new therapeutics in autoimmune diseases, with many more in earlier stages of development for a wide variety of diseases, such as fibrotic disorders, vascular diseases, and cancer.

The ubiquitin ligation machinery in the defense against bacterial pathogens.

The ubiquitin system is an important part of the host cellular defense program during bacterial infection. This is in particular evident for a number of bacteria including Salmonella Typhimurium and Mycobacterium tuberculosis which—inventively as part of their invasion strategy or accidentally upon rupture of seized host endomembranes—become exposed to the host cytosol. Ubiquitylation is involved in the detection and clearance of these bacteria as well as in the activation of innate immune and inflammatory signaling. Remarkably, all these defense responses seem to emanate from a dense layer of ubiquitin which coats the invading pathogens. In this review, we focus on the diverse group of host cell E3 ubiquitin ligases that help to tailor this ubiquitin coat. In particular, we address how the divergent ubiquitin conjugation mechanisms of these ligases contribute to the complexity of the anti‐bacterial coating and the recruitment of different ubiquitin‐binding effectors. We also discuss the activation and coordination of the different E3 ligases and which strategies bacteria evolved to evade the activities of the host ubiquitin system.

C-REV Retains High Infectivity Regardless of the Expression Levels of cGAS and STING in Cultured Pancreatic Cancer Cells.

Oncolytic virus (OV) therapy is widely considered as a major breakthrough in anti-cancer treatments. In our previous study, the efficacy and safety of using C-REV for anti-cancer therapy in patients during stage I clinical trial was reported. The stimulator of interferon genes (STING)–TBK1–IRF3–IFN pathway is known to act as the central cellular host defense against viral infection. Recent reports have linked low expression levels of cGAS and STING in cancer cells to poor prognosis among patients. Moreover, downregulation of cGAS and STING has been linked to higher susceptibility to OV infection among several cancer cell lines. In this paper, we show that there is little correlation between levels of cGAS/STING expression and susceptibility to C-REV among human pancreatic cancer cell lines. Despite having a responsive STING pathway, BxPC-3 cells are highly susceptible to C-REV infection. Upon pre-activation of the STING pathway, BxPc-3 cells exhibited resistance to C-REV infection. However, without pre-activation, C-REV completely suppressed the STING pathway in BxPC-3 cells. Additionally, despite harboring defects in the STING pathway, other high-grade cancer cell lines, such as Capan-2, PANC-1 and MiaPaCa-2, still exhibited low susceptibility to C-REV infection. Furthermore, overexpression of STING in MiaPaCa-2 cells altered susceptibility to a limited extent. Taken together, our data suggest that the cGAS–STING pathway plays a minor role in the susceptibility of pancreatic cancer cell lines to C-REV infection.

Engineered Sulfated Polysaccharides for Biomedical Applications

AbstractSulfated polysaccharides are ubiquitous in living systems and have central roles in biological functions such as organism development, cell proliferation and differentiation, cellular communication, tissue homeostasis, and host defense. Engineered sulfated polysaccharides (ESPs) are structural derivatives not found in nature but generated through chemical and enzymatic modification of natural polysaccharides, as well as chemically synthesized oligo‐ and polysaccharides. ESPs exhibit novel and augmented biological properties compared with their unmodified counterparts, mainly through facilitating interactions with other macromolecules. These interactions are closely linked to their sulfation patterns and backbone structures, providing a means to fine‐tune biological properties and characterize structural–functional relationships by employing well‐characterized polysaccharides and strategies for regioselective modification. The following review provides a comprehensive overview of the synthesis and characterization of ESPs and of their biological properties. Through the pioneering research presented here, key emerging application areas for ESPs, which can lead to novel breakthroughs in biomedical research and clinical treatments, are highlighted.

Immunopathogenicity of Acanthamoeba spp. in the Brain and Lungs.

Free-living amoebas, including Acanthamoeba spp., are widely distributed in soil, water, and air. They are capable of causing granulomatous amebic encephalitis, Acanthamoeba pneumonia, Acanthamoeba keratitis, and disseminated acanthamoebiasis. Despite low occurrence worldwide, the mortality rate of Acanthamoeba spp. infections is very high, especially in immunosuppressed hosts. Acanthamoeba infections are a medical problem, owing to limited improvement in diagnostics and treatment, which is associated with incomplete knowledge of pathophysiology, pathogenesis, and the host immune response against Acanthamoeba spp. infection. The aim of this review is to present the biochemical and molecular mechanisms of Acanthamoeba spp.–host interactions, including the expression of Toll-like receptors, mechanisms of an immune response, the activity of metalloproteinases, the secretion of antioxidant enzymes, and the expression and activity of cyclooxygenases. We show the relationship between Acanthamoeba spp. and the host at the cellular level and host defense reactions that lead to changes in the selected host’s organs.

Semi-Quantitative Analysis of Peptidoglycan by Liquid Chromatography Mass Spectrometry and Bioinformatics.

Peptidoglycan is an important component of bacterial cell walls and a common cellular target for antimicrobials. Although aspects of peptidoglycan structure are fairly conserved across all bacteria, there is also considerable variation between Gram-positives/negatives and between species. In addition, there are numerous known variations, modifications, or adaptations to the peptidoglycan that can occur within a bacterial species in response to growth phase and/or environmental stimuli. These variations produce a highly dynamic structure that is known to participate in many cellular functions, including growth/division, antibiotic resistance, and host defense avoidance. To understand the variation within peptidoglycan, the overall structure must be broken down into its constitutive parts (known as muropeptides) and assessed for overall cellular composition. Peptidoglycomics uses advanced mass spectrometry combined with high-powered bioinformatic data analysis to examine peptidoglycan composition in fine detail. The following protocol describes the purification of peptidoglycan from bacterial cultures, the acquisition of muropeptide intensity data through a liquid chromatograph-mass spectrometer, and the differential analysis of peptidoglycan composition using bioinformatics.

Transcriptomic analyses reveal comprehensive responses of insect hemocytes to mycopathogen Beauveria bassiana, and fungal virulence-related cell wall protein assists pathogen to evade host cellular defense

ABSTRACT Entomopathogenic fungi naturally infect insect hosts in environment. Fungal invasion and host immune defense are still in the progress of co-evolution. In this study, entomopathogenic fungus Beauveria bassiana and lepidopteran insect Galleria mellonella were used to investigate host cellular immunity and fungal strategy to evade host defense. First of all, genome-wide expression revealed the transcriptomic responses of hemocytes to insect mycopathogen, which dynamically varied during infection process. Enrichment analysis indicated that differentially expressed genes were primarily involved in metabolism, cellular process and immune system. Notably, cellular response involved a series of hydrolytic enzyme and antimicrobial peptide genes which were sorted together in clustering analysis. In B. bassiana, a cell-wall protein gene (BbCwp) contributes to fungal development in host hemocoel and virulence. RT-qPCR analyses indicated that infection by ΔBbCwp mutant strain caused the up-regulated expression of a series of immunity-related genes, including β-1, 3-glucan recognition protein, hydrolytic enzyme and antimicrobial peptide genes. Disruption of BbCwp resulted in a significant change in conidial lectin-binding feature and the enhanced encapsulation by the host hemocytes. After being treated with hydrolytic enzymes, ΔBbCwp mutant displayed a significantly enhanced sensitivity to osmotic and oxidative stresses. In conclusion, fungal invasion initiates comprehensive physiological responses in the host hemocytes. For mycopathogen, cell-wall protein plays an important role in fungal evasion of immunity defense and colonization in host. Our studies provide an initial framework for exploring more mechanistic details about the fungus–host interaction.

Non-Coding RNAs: Strategy for Viruses' Offensive.

The awareness of viruses as a constant threat for human public health is a matter of fact and in this resides the need of understanding the mechanisms they use to trick the host. Viral non-coding RNAs are gaining much value and interest for the potential impact played in host gene regulation, acting as fine tuners of host cellular defense mechanisms. The implicit importance of v-ncRNAs resides first in the limited genomes size of viruses carrying only strictly necessary genomic sequences. The other crucial and appealing characteristic of v-ncRNAs is the non-immunogenicity, making them the perfect expedient to be used in the never-ending virus-host war. In this review, we wish to examine how DNA and RNA viruses have evolved a common strategy and which the crucial host pathways are targeted through v-ncRNAs in order to grant and facilitate their life cycle.