Identification and Profiling of a Novel Bombyx mori latent virus Variant Acutely Infecting Helicoverpa armigera and Trichoplusia ni.

Insect cell expression systems are increasingly being used in the medical industry to develop vaccines against diseases such as COVID-19. However, viral infections are common in these systems, making it necessary to thoroughly characterize the viruses present. One such virus is Bombyx mori latent virus (BmLV), which is known to be specific to Bombyx mori and to have low pathogenicity. However, there has been little research on the tropism and virulence of BmLV. In this study, we examined the genomic diversity of BmLV and identified a variant that persistently infects Trichoplusia ni-derived High Five cells. We also assessed the pathogenicity of this variant and its effects on host responses using both in vivo and in vitro systems. Our results showed that this BmLV variant causes acute infections with strong cytopathic effects in both systems. Furthermore, we characterized the RNAi-based immune response in the T. ni cell line and in Helicoverpa armigera animals by assessing the regulation of RNAi-related genes and profiling the generated viral small RNAs. Overall, our findings shed light on the prevalence and infectious properties of BmLV. We also discuss the potential impact of virus genomic diversity on experimental outcomes, which can help interpret past and future research results.

Autoantibodies to Interferons in Infectious Diseases.

Anti-cytokine autoantibodies and, in particular, anti-type I interferons are increasingly described in association with immunodeficient, autoimmune, and immune-dysregulated conditions. Their presence in otherwise healthy individuals may result in a phenotype characterized by a predisposition to infections with several agents. For instance, anti-type I interferon autoantibodies are implicated in Coronavirus Disease 19 (COVID-19) pathogenesis and found preferentially in patients with critical disease. However, autoantibodies were also described in the serum of patients with viral, bacterial, and fungal infections not associated with COVID-19. In this review, we provide an overview of anti-cytokine autoantibodies identified to date and their clinical associations; we also discuss whether they can act as enemies or friends, i.e., are capable of acting in a beneficial or harmful way, and if they may be linked to gender or immunosenescence. Understanding the mechanisms underlying the production of autoantibodies could improve the approach to treating some infections, focusing not only on pathogens, but also on the possibility of a low degree of autoimmunity in patients.

Host Defenses to Viruses

Virus infections continue to pose a substantial threat to human health. A prime example is the ongoing 2019 coronavirus pandemic caused by the novel virus SARS-CoV-2. Unraveling the intricacies of immune defenses against viruses should lead to improved control of infections through the design of new vaccines and therapies. Our understanding of the fundamental cellular and molecular mechanisms involved in the immune system's response to virus infection has improved substantially in recent years. This wealth of new information and the promise of new insight from systems biology approaches continue to drive research in this field. Such knowledge has revealed why viruses sometimes induce immune dysfunction or trigger disastrous pathology and has paved the way for new therapies being tested against chronic and emerging infections. In this chapter, we briefly summarize the general concepts in immunity to virus infections and highlight some of the key challenges remaining for the future. Virus infections continue to pose a substantial threat to human health, and many cannot be controlled effectively with current vaccines or antiviral approaches. © 2023 Elsevier Ltd. All rights reserved.

Mechanisms of impairment of interferon production by SARS-CoV-2.

Interferons (IFNs) are crucial components of the cellular innate immune response to viral infections. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a remarkable capacity to suppress the host IFN production to benefit viral replication and spread. Thus far, of the 28 known virus-encoded proteins, 16 have been found to impair the host's innate immune system at various levels ranging from detection and signaling to transcriptional and post-transcriptional regulation of expression of the components of the cellular antiviral response. Additionally, there is evidence that the viral genome encodes non-protein-coding microRNA-like elements that could also target IFN-stimulated genes. In this brief review, we summarise the current state of knowledge regarding the factors and mechanisms by which SARS-CoV-2 impairs the production of IFNs and thereby dampens the host's innate antiviral immune response.

Porcine epidemic diarrhea virus (PEDV) ORF3 protein inhibits cellular type I interferon signaling through down-regulating proteins expression in RLRs-mediated pathway.

Porcine epidemic diarrhea virus (PEDV) is an entero-pathogenic coronavirus, which belongs to the genus Alphacoronavirus in the family Coronaviridae, causing lethal watery diarrhea in piglets. Previous studies have shown that PEDV has developed an antagonistic mechanism by which it evades the antiviral activities of interferon (IFN), such as the sole accessory protein open reading frame 3 (ORF3) being found to inhibit IFN-ß promoter activities, but how this mechanism used by PEDV ORF3 inhibits activation of the type I signaling pathway remains not fully understood. Thus, in this present study, we showed that PEDV ORF3 inhibited both polyinosine-polycytidylic acid (poly(I:C))- and IFNα2b-stimulated transcription of IFN-ß and interferon-stimulated genes (ISGs) mRNAs. The expression levels of antiviral proteins in the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mediated pathway was down-regulated in cells with over-expression of PEDV ORF3 protein, but global protein translation remained unchanged and the association of ORF3 with RLRs-related antiviral proteins was not detected, implying that ORF3 only specifically suppressed the expression of these signaling molecules. At the same time, we also found that the PEDV ORF3 protein inhibited interferon regulatory factor 3 (IRF3) phosphorylation and poly(I:C)-induced nuclear translocation of IRF3, which further supported the evidence that type I IFN production was abrogated by PEDV ORF3 through interfering with RLRs signaling. Furthermore, PEDV ORF3 counteracted transcription of IFN-ß and ISGs mRNAs, which were triggered by over-expression of signal proteins in the RLRs-mediated pathway. However, to our surprise, PEDV ORF3 initially induced, but subsequently reduced the transcription of IFN-ß and ISGs mRNAs to normal levels. Additionally, mRNA transcriptional levels of signaling molecules located at IFN-ß upstream were not inhibited, but elevated by PEDV ORF3 protein. Collectively, these results demonstrate that inhibition of type I interferon signaling by PEDV ORF3 can be realized through down-regulating the expression of signal molecules in the RLRs-mediated pathway, but not via inhibiting their mRNAs transcription. This study points to a new mechanism evolved by PEDV through blockage of the RLRs-mediated pathway by ORF3 protein to circumvent the host's antiviral immunity.

Non-coding RNAs derived from the foot-and-mouth disease virus genome trigger broad antiviral activity against coronaviruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a potentially severe respiratory disease, the coronavirus disease 2019 (COVID-19), an ongoing pandemic with limited therapeutic options. Here, we assessed the anti-coronavirus activity of synthetic RNAs mimicking specific domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome (ncRNAs). These molecules are known to exert broad-spectrum antiviral activity in cell culture, mice and pigs effectively triggering the host innate immune response. The ncRNAs showed potent antiviral activity against SARS-CoV-2 after transfection in human intestinal Caco-2 and lung epithelium Calu-3 2B4 cells. When the in vivo efficacy of the FMDV ncRNAs was assessed in K18-hACE2 mice, administration of naked ncRNA before intranasal SARS-CoV-2 infection significantly decreased the viral load and the levels of pro-inflammatory cytokines in the lungs compared with untreated infected mice. The ncRNAs were also highly efficacious when assayed against common human HCoV-229E and porcine transmissible gastroenteritis virus (TGEV) in hepatocyte-derived Huh-7 and swine testis ST cells, respectively. These results are a proof of concept of the pan-coronavirus antiviral activity of the FMDV ncRNAs including human and animal divergent coronaviruses and potentially enhance our ability to fight future emerging variants.

Molecular Understanding of ACE-2 and HLA-Conferred Differential Susceptibility to COVID-19: Host-Directed Insights Opening New Windows in COVID-19 Therapeutics.

The genetic variants of HLAs (human leukocyte antigens) play a crucial role in the virus-host interaction and pathology of COVID-19. The genetic variants of HLAs not only influence T cell immune responses but also B cell immune responses by presenting a variety of peptide fragments of invading pathogens. Peptide cocktail vaccines produced by using various conserved HLA-A2 epitopes provoke substantial specific CD8+ T cell responses in experimental animals. The HLA profiles vary among individuals and trigger different T cell-mediated immune responses in COVID-19 infections. Those with HLA-C*01 and HLA-B*44 are highly susceptible to the disease. However, HLA-A*02:01, HLA-DR*03:01, and HLA-Cw*15:02 alleles show resistance to SARS infection. Understanding the genetic association of HLA with COVID-19 susceptibility and severity is important because it can help in studying the transmission of COVID-19 and its physiopathogenesis. The HLA-C*01 and B*44 allele pathways can be studied to gain insight into disease transmission and physiopathogenesis. Therefore, integrating HLA testing is suggested in the ongoing pandemic, which will help in the rapid identification of highly susceptible populations worldwide and possibly acclimate vaccine development. Therefore, understanding the correlation between HLA and SARS-CoV-2 is critical in opening new insights into COVID-19 therapeutics, based on previous studies conducted.

Single-cell RNA-seq methods to interrogate virus-host interactions.

The twenty-first century has seen the emergence of many epidemic and pandemic viruses, with the most recent being the SARS-CoV-2-driven COVID-19 pandemic. As obligate intracellular parasites, viruses rely on host cells to replicate and produce progeny, resulting in complex virus and host dynamics during an infection. Single-cell RNA sequencing (scRNA-seq), by enabling broad and simultaneous profiling of both host and virus transcripts, represents a powerful technology to unravel the delicate balance between host and virus. In this review, we summarize technological and methodological advances in scRNA-seq and their applications to antiviral immunity. We highlight key scRNA-seq applications that have enabled the understanding of viral genomic and host response heterogeneity, differential responses of infected versus bystander cells, and intercellular communication networks. We expect further development of scRNA-seq technologies and analytical methods, combined with measurements of additional multi-omic modalities and increased availability of publicly accessible scRNA-seq datasets, to enable a better understanding of viral pathogenesis and enhance the development of antiviral therapeutics strategies.

Multipolymer microsphere delivery of SARS-CoV-2 antigens.

Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. STATEMENT OF SIGNIFICANCE: Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics.

RNA INTERFERENCE IS THE BASIS OF HUMAN ANTIVIRAL DEFENSE.

Comparative analysis of antiviral protective mechanisms in protozoa and RNA interference of multicellular organisms has revealed their similarity, also providing a clue to understanding the adaptive immunity. In this article, we present the latest evidence on the importance of RNA-guided gene regulation in human antiviral defense. The role of neutralizing antibodies and interferon system in viral invasion is considered. The new concept has been introduced, i.e., antiviral protection of any living organism is based on the intracellular RNA-guided mechanisms. Simple and effective defense against viruses is that spacer segment of the viral DNA is inserted into the cellular chromosomes. Upon re-infection, the RNA transcript of the spacer directs nuclease enzymes against the foreign genome. This is a really adaptive immune defense that any cell potentially possesses. In humans, the interferon system provides an additional tool for early suppression of viral infections which shifts the cells to the alert regimen, thus preventing further spread of infection. The main task of the human central immune system is to maintain integrity and combat foreign organisms. Accordingly, a suitable index of acquired antiviral immunity should be a presence of specific spacer markers in DNA samples from reconvalescent persons, rather than detection of neutralizing antibodies, B and T memory cells. This article is addressed primarily to general medical community, and its practical conclusions are as follows: 1. Presence or absence of specific antibodies to SARS-CoV-2 is not a prognostic sign of the disease. Detection of specific antibodies in blood simply reflects the fact that the person has contacted with the viral agent. Absence of antibodies does not mean a lack of such contact, and the persons with high titers of specific antibodies are not protected from re-infection with SARS-CoV-2. 2. PCR testing: The PCR results may remain "false positive" in those subjects who have had COVID-19, if the genetic material is taken from the site of initial virus contraction (mainly, nasopharynx). In our opinion, negative PCR tests for COVID-19 in blood plasma and urine will be a more correct index for the absence of the disease, even with positive PCR tests from the nasopharyngeal samples. 3. It is necessary to draw attention of general practitioners to potential usage of retinol in prevention and treatment of COVID-19, given the importance of RLR receptors in recognition of viral RNAs and positive experience of vitamin A administration in measles, another dangerous viral disease. Copyright © 2022, SPb RAACI.

RNA INTERFERENCE IS THE BASIS OF HUMAN ANTIVIRAL DEFENSE

Comparative analysis of antiviral protective mechanisms in protozoa and RNA interference of multicellular organisms has revealed their similarity, also providing a clue to understanding the adaptive immunity. In this article, we present the latest evidence on the importance of RNA-guided gene regulation in human antiviral defense. The role of neutralizing antibodies and interferon system in viral invasion is considered. The new concept has been introduced, i.e., antiviral protection of any living organism is based on the intracellular RNA-guided mechanisms. Simple and effective defense against viruses is that spacer segment of the viral DNA is inserted into the cellular chromosomes. Upon re-infection, the RNA transcript of the spacer directs nuclease enzymes against the foreign genome. This is a really adaptive immune defense that any cell potentially possesses. In humans, the interferon system provides an additional tool for early suppression of viral infections which shifts the cells to the alert regimen, thus preventing further spread of infection. The main task of the human central immune system is to maintain integrity and combat foreign organisms. Accordingly, a suitable index of acquired antiviral immunity should be a presence of specific spacer markers in DNA samples from reconvalescent persons, rather than detection of neutralizing antibodies, B and T memory cells. This article is addressed primarily to general medical community, and its practical conclusions are as follows: 1. Presence or absence of specific antibodies to SARS-CoV-2 is not a prognostic sign of the disease. Detection of specific antibodies in blood simply reflects the fact that the person has contacted with the viral agent. Absence of antibodies does not mean a lack of such contact, and the persons with high titers of specific antibodies are not protected from re-infection with SARS-CoV-2. 2. PCR testing: The PCR results may remain "false positive” in those subjects who have had COVID-19, if the genetic material is taken from the site of initial virus contraction (mainly, nasopharynx). In our opinion, negative PCR tests for COVID-19 in blood plasma and urine will be a more correct index for the absence of the disease, even with positive PCR tests from the nasopharyngeal samples. 3. It is necessary to draw attention of general practitioners to potential usage of retinol in prevention and treatment of COVID-19, given the importance of RLR receptors in recognition of viral RNAs and positive experience of vitamin A administration in measles, another dangerous viral disease. © 2022, SPb RAACI.

Host microRNAs exhibit differential propensity to interact with SARS-CoV-2 and variants of concern.

A significant number of SARS-CoV-2-infected individuals naturally overcome viral infection, suggesting the existence of a potent endogenous antiviral mechanism. As an innate defense mechanism, microRNA (miRNA) pathways in mammals have evolved to restrict viruses, besides regulating endogenous mRNAs. In this study, we systematically examined the complete repertoire of human miRNAs for potential binding sites on SARS-CoV-2 Wuhan-Hu-1, Beta, Delta, and Omicron. Human miRNA and viral genome interaction were analyzed using RNAhybrid 2.2 with stringent parameters to identify highly bonafide miRNA targets. Using publicly available data, we filtered for miRNAs expressed in lung epithelial cells/tissue and oral keratinocytes, concentrating on the miRNAs that target SARS-CoV-2 S protein mRNAs. Our results show a significant loss of human miRNA and SARS-CoV-2 interactions in Omicron (130 miRNAs) compared to Wuhan-Hu-1 (271 miRNAs), Beta (279 miRNAs), and Delta (275 miRNAs). In particular, hsa-miR-3150b-3p and hsa-miR-4784 show binding affinity for S protein of Wuhan strain but not Beta, Delta, and Omicron. Loss of miRNA binding sites on N protein was also observed for Omicron. Through Ingenuity Pathway Analysis (IPA), we examined the experimentally validated and highly predicted functional role of these miRNAs. We found that hsa-miR-3150b-3p and hsa-miR-4784 have several experimentally validated or highly predicted target genes in the Toll-like receptor, IL-17, Th1, Th2, interferon, and coronavirus pathogenesis pathways. Focusing on the coronavirus pathogenesis pathway, we found that hsa-miR-3150b-3p and hsa-miR-4784 are highly predicted to target MAPK13. Exploring miRNAs to manipulate viral genome/gene expression can provide a promising strategy with successful outcomes by targeting specific VOCs.

SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D.

Natural killer (NK) cells are cytotoxic effector cells that target and lyse virally infected cells; many viruses therefore encode mechanisms to escape such NK cell killing. Here, we interrogate the ability of SARS-CoV-2 to modulate NK cell recognition and lysis of infected cells. We find that NK cells exhibit poor cytotoxic responses against SARS-CoV-2-infected targets, preferentially killing uninfected bystander cells. We demonstrate that this escape is driven by downregulation of ligands for the activating receptor NKG2D (NKG2D-L). Indeed, early in viral infection, prior to NKG2D-L downregulation, NK cells are able to target and kill infected cells; however, this ability is lost as viral proteins are expressed. Finally, we find that SARS-CoV-2 non-structural protein 1 (Nsp1) mediates downregulation of NKG2D-L and that Nsp1 alone is sufficient to confer resistance to NK cell killing. Collectively, our work demonstrates that SARS-CoV-2 evades direct NK cell cytotoxicity and describes a mechanism by which this occurs.

AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.

Antiviral function and viral antagonism of the rapidly evolving dynein activating adaptor NINL.

Viruses interact with the intracellular transport machinery to promote viral replication. Such host-virus interactions can drive host gene adaptation, leaving signatures of pathogen-driven evolution in host genomes. Here, we leverage these genetic signatures to identify the dynein activating adaptor, ninein-like (NINL), as a critical component in the antiviral innate immune response and as a target of viral antagonism. Unique among genes encoding components of active dynein complexes, NINL has evolved under recurrent positive (diversifying) selection, particularly in its carboxy-terminal cargo-binding region. Consistent with a role for NINL in host immunity, we demonstrate that NINL knockout cells exhibit an impaired response to interferon, resulting in increased permissiveness to viral replication. Moreover, we show that proteases encoded by diverse picornaviruses and coronaviruses cleave and disrupt NINL function in a host- and virus-specific manner. Our work reveals the importance of NINL in the antiviral response and the utility of using signatures of host-virus genetic conflicts to uncover new components of antiviral immunity and targets of viral antagonism.

Humans and viruses are locked in an evolutionary arms race. Viruses hijack cells, using their resources and proteins to build more viral particles; the cells fight back, calling in the immune system to fend off the attack. Both actors must constantly and quickly evolve to keep up with each other. This genetic conflict has been happening for millions of years, and the indelible marks it has left on genes can serve to uncover exactly how viruses interact with the organisms they invade. One hotspot in this host-virus conflict is the complex network of molecules that help to move cargo inside a cell. This system transports elements of the immune system, but viruses can also harness it to make more of themselves. Scientists still know very little about how viruses and the intracellular transport machinery interact, and how this impacts viral replication and the immune response. Stevens et al. therefore set out to identify new interactions between viruses and the transport system by using clues left in host genomes by evolution. They focused on dynein, a core component of this machinery which helps to haul molecular actors across a cell. To do so, dynein relies on adaptor molecules such as 'Ninein-like', or NINL for short. Closely examining the gene sequence for NINL across primates highlighted an evolutionary signature characteristic of host-virus genetic conflicts; this suggests that the protein may be used by viruses to reproduce, or by cells to fend off infection. And indeed, human cells lacking the NINL gene were less able to defend themselves, allowing viruses to grow much faster than normal. Further work showed that NINL was important for a major type of antiviral immune response. As a potential means to sabotage this defence mechanism, some viruses cleave NINL at specific sites and disrupt its role in intracellular transport. Better antiviral treatments are needed to help humanity resist old foes and new threats alike. The work by Stevens et al. demonstrates how the information contained in host genomes can be leveraged to understand what drives susceptibility to an infection, and to pinpoint molecular actors which could become therapeutic targets.

Dual Roles of Tumor Necrosis Factor Superfamily 14 in Antiviral Immunity.

Tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) is an interesting costimulatory molecule associated with T lymphocyte activation, and it mainly exerts its biological effects by binding to its receptors herpesvirus invasion mediator (HVEM) and lymphotoxin-ß receptor. Research shows that TNFSF14 plays a critical regulatory role in immune responses to viral infection, but its role is different in different diseases. TNFSF14 can be a cytokine neutralization target during novel coronavirus infection, and anti-TNFSF14 monoclonal antibody treatment can reduce the risk of respiratory failure and mortality. When the host is infected with adenovirus, TNFSF14 can be used as an inflammatory biomarker to indicate whether there was an adenovirus infection in the host and the degree of disease caused by viral infection. When hosts suffer influenza virus infection, the TNFSF14-HVEM signaling pathway can stimulate the maturation and proliferation of memory CD8+ T cells, which helps the host immune system stimulate a second immune response against respiratory virus infection. TNFSF14 can act as an immune adjuvant and enhance the immunogenicity of the human papillomavirus (HPV) DNA vaccine when the host is infected with HPV. During hepatitis virus infection, TNFSF14 acts as a proinflammatory factor, participates in inflammation and causes tissue damage. In conclusion, TNFSF14 plays different and significant roles in diverse viral infections. This article reviews the current research on TNFSF14 in antiviral immunity.

Microbiota regulation of viral infections through interferon signaling.

The interferon (IFN) response is the major early innate immune response against invading viral pathogens and is even capable of mediating sterilizing antiviral immunity without the support of the adaptive immune system. Cumulative evidence suggests that the gut microbiota can modulate IFN responses, indirectly determining virological outcomes. This review outlines our current knowledge of the interactions between the gut microbiota and IFN responses and dissects the different mechanisms by which the gut microbiota may alter IFN expression to diverse viral infections. This knowledge offers a basis for translating experimental evidence from animal studies into the human context and identifies avenues for leveraging the gut microbiota-IFN-virus axis to improve control of viral infections and performance of viral vaccines.

Potential Neuroinvasion Mechanism of SARS-CoV-2

The severe acute respiratory syndrome coronavirus-2, a coronavirus, is known to cause acute respiratory distress syndrome and a range of non)respiratory effects, particularly in elderly male patients with underlying health conditions such overweight, diabetes, and hypertension. The coronavirus disease-2019 sequelae include multiple organ failure and neurological issues, and these prior health issues are linked to endothelial dysfunction. Although inhalation is the most frequent mode of infection, this virus has also been discovered in neurons, cerebrospinal fluid, the choroid plexus, and meningeal vasculature (English) [ FROM AUTHOR] Bir koronavirüs olan şiddetli akut solunum yolu sendromu koronavirüsü-2’nin, özellikle obezite, diyabet ve hipertansiyon gibi sağlık sorunları olan yaşlı erkek hastalarda akut solunum sıkıntısı sendromuna ve bir dizi solunum dışı sekellere neden olduğu bilinmektedir. Bu sağlık sorunları endotel disfonksiyonla bağlantılıdır ve koronavirüs hastalığı-2019 sekelleri, çoklu organ yetmezliği ve nörolojik sorunları içerir. Solunum birincil enfeksiyon modu olsa da, bu virüs koroid pleksus ve meningeal arterlerin yanı sıra nöronlar ve beyin omurilik sıvısı dahil olmak üzere çeşitli organlarda keşfedilmiştir (Turkish) [ FROM AUTHOR] Copyright of Turkish Journal of Immunology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Delivery of MERS antigen encapsulated in α-GalCer-bearing liposomes elicits stronger antigen-specific immune responses.

Alpha-Galactosylceramide (α-GalCer) effectively activates the natural killer T (NKT) cells to secrete remarkable amounts of Th1 and Th2 cytokines and therefore, acts as a potential immunoadjuvant in vaccine formulation. In the present study, we prepared α-GalCer-bearing or α-GalCer-free liposomes and loaded them with Middle East Respiratory Syndrome Coronavirus papain-like protease (α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro). These formulations were injected in mice to investigate the antigen-specific humoral and cell-mediated immune responses. The immunisation with α-GalCer-Lip-MERS-CoV PLpro or Lip-MERS-CoV PLpro did not induce any notable toxicity in immunised mice. The results demonstrated that mice immunised with α-GalCer-Lip-MERS-CoV PLpro showed greater antigen-specific antibody titre, switching of IgG isotyping to IgG2a subclass and higher lymphocyte proliferation. Moreover, the splenocytes from α-GalCer-Lip-MERS-CoV PLpro immunised mice secreted greater levels of IFN-γ, IL-4, IL-2 and IL-12. Interestingly, a booster dose induced stronger memory immune responses in mice previously immunised with α-GalCer-Lip-MERS-CoV PLpro. In summary, α-GalCer-Lip-MERS-CoV PLpro may prove to be a promising vaccine formulation to protect the individuals against MERS-CoV infection.

XAF1 Protects Host against Emerging RNA Viruses by Stabilizing IRF1-Dependent Antiviral Immunity.

XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.