scholarly journals Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity

2020 ◽  
Author(s):  
Mohamed Bayoumi Fahmy Hawash ◽  
Joaquin Sanz-Remón ◽  
Jean-Christophe Grenier ◽  
Jordan Kohn ◽  
Vania Yotova ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Relatedness ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Potential Cost ◽  
Viral Pathogens ◽  
Increased Sensitivity ◽  
Bacterial Stimulation ◽  
Interferon Responses

AbstractDespite their close genetic relatedness, apes and African and Asian monkeys (AAMs), strongly differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of inter-species differences in immune response to infection. However, due to the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole genome transcriptomic responses of ape species (human, common chimpanzee) and AAMs (rhesus macaque and olive baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, upregulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

scholarly journals Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity

2021 ◽  
Vol 118 (13) ◽  
pp. e2015855118
Author(s):  
Mohamed B. F. Hawash ◽  
Joaquin Sanz-Remón ◽  
Jean-Christophe Grenier ◽  
Jordan Kohn ◽  
Vania Yotova ◽  
...  
Keyword(s):  
Immune Response ◽  
Genetic Relatedness ◽  
Viral Infections ◽  
Transcriptional Response ◽  
Transcriptional Responses ◽  
Potential Cost ◽  
Viral Pathogens ◽  
Increased Sensitivity ◽  
Bacterial Stimulation ◽  
Interferon Responses

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

scholarly journals Transcriptional analysis of lymphoid tissues from infected nonhuman primates reveals the basis for attenuation and immunogenicity of an Ebola virus encoding a mutant VP35 protein

2021 ◽  
Author(s):  
Amanda Pinski ◽  
Courtney Woolsey ◽  
Allen Jankeel ◽  
Robert Cross ◽  
Christopher F. Basler ◽  
...  
Keyword(s):  
Immune Response ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
Transcriptional Response ◽  
Transcriptional Analysis ◽  
Lymphoid Tissues ◽  
High Dose ◽  
Type I ◽  
Wild Type ◽  
Transcriptional Responses

Infection with Zaire ebolavirus (EBOV), a member of the Filoviridae family, causes a disease characterized by high levels of viremia, aberrant inflammation, coagulopathy, and lymphopenia. EBOV initially replicates in lymphoid tissues and disseminates via dendritic cells (DCs) and monocytes to liver, spleen, adrenal gland and other secondary organs. EBOV protein VP35 is a critical immune evasion factor that inhibits type I interferon signaling and DC maturation. Nonhuman primates immunized with a high dose (5x105 PFU) of recombinant EBOV containing a mutated VP35 (VP35m) are protected from challenge with wild-type (wt)EBOV. This protection is accompanied by a transcriptional response in the peripheral blood reflecting a regulated innate immune response and a robust induction of adaptive immune genes. However, the host transcriptional response to VP35m in lymphoid tissues has not been evaluated. Therefore, we conducted a transcriptional analysis of axillary and inguinal lymph nodes, and spleen tissues of NHPs infected with a low dose (2x104 PFU) of VP35m and then backchallenged with a lethal dose of wtEBOV. VP35m induced early transcriptional responses in lymphoid tissues that are distinct from those observed in wtEBOV challenge. Specifically, we detected robust antiviral innate and adaptive responses and fewer transcriptional changes in genes with roles in angiogenesis, apoptosis and inflammation. Two of three macaques survived wtEBOV backchallenge, with only the nonsurvivor displaying a transcriptional response reflecting Ebola virus disease. These data suggest that VP35 is a key modulator of early host responses in lymphoid tissues, thereby regulating disease progression and severity following EBOV challenge. IMPORTANCE Zaire Ebola virus (EBOV) infection causes a severe and often fatal disease characterized by inflammation, coagulation defects, and organ failure driven by a defective host immune response. Lymphoid tissues are key sites of EBOV pathogenesis and generation of an effective immune response to infection. A recent study demonstrated that infection with an EBOV encoding a mutant VP35, a viral protein that antagonizes host immunity, can protect nonhuman primates (NHPs) against lethal EBOV challenge. However, no studies have examined the response to this mutant EBOV in lymphoid tissues. Here, we characterize the gene expression of lymphoid tissues from NHPs challenged with the mutant EBOV and subsequently with wild-type EBOV to identify signatures of a protective host response. Our findings are critical for elucidating viral pathogenesis, mechanisms of host antagonism and the role of lymphoid organs in protective responses to EBOV to improve the development of antivirals and vaccines against EBOV.

scholarly journals Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2410
Author(s):  
Giorgio Costagliola ◽  
Giulia Nuzzi ◽  
Erika Spada ◽  
Pasquale Comberiati ◽  
Elvira Verduci ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Coenzyme Q ◽  
Antimicrobial Effect ◽  
Common Element ◽  
Viral Pathogens ◽  
Differentiation And Proliferation ◽  
Pro Inflammatory Cytokines

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.

The Immune Response to Respiratory Viruses: From Start to Memory

2021 ◽  
Vol 42 (06) ◽  
pp. 759-770
Author(s):  
Tom D.Y. Reijnders ◽  
Alex R. Schuurman ◽  
Tom van der Poll
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Viral Pathogens ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Destructive Inflammation ◽  
Systemic Memory

AbstractBiomedical research has long strived to improve our understanding of the immune response to respiratory viral infections, an effort that has become all the more important as we live through the consequences of a pandemic. The disease course of these infections is shaped in large part by the actions of various cells of the innate and adaptive immune systems. While these cells are crucial in clearing viral pathogens and establishing long-term immunity, their effector mechanisms may also escalate into excessive, tissue-destructive inflammation detrimental to the host. In this review, we describe the breadth of the immune response to infection with respiratory viruses such as influenza and respiratory syncytial virus. Throughout, we focus on the host rather than the pathogen and try to describe shared patterns in the host response to different viruses. We start with the local cells of the airways, onto the recruitment and activation of innate and adaptive immune cells, followed by the establishment of local and systemic memory cells key in protection against reinfection. We end by exploring how respiratory viral infections can predispose to bacterial superinfection.

Respiratory and gastrointestinal epithelial modulation of the immune response during viral infection

2011 ◽  
Vol 18 (1) ◽  
pp. 179-189 ◽  
Author(s):  
Paul M Fitch ◽  
Paul Henderson ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Human Body ◽  
World Wide ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Significant Morbidity ◽  
Viral Pathogens ◽  
Adaptive Immune ◽  
Adaptive Interface ◽  
Portal Of Entry

Respiratory and enteric viral infections cause significant morbidity and mortality world-wide and represent a major socio-economic burden. Many of these viruses have received unprecedented public and media interest in recent years. A popular public misconception is that viruses are a threat to which the human body has only limited defences. However, the majority of primary and secondary exposures to virus are asymptomatic or induce only minor symptoms. The mucosal epithelial surfaces are the main portal of entry for viral pathogens and are centrally involved in the initiation, maintenance and polarisation of the innate and adaptive immune response to infection. This review describes the defences employed by the epithelium of the respiratory and gastrointestinal tracts during viral infections with focus on epithelial modulation of the immune response at the innate/adaptive interface.

scholarly journals Switching Sides: How Endogenous RetrovirusesProtect us from Viral Infections

2021 ◽  
Author(s):  
Smitha Srinivasachar Badarinarayan ◽  
Daniel Sauter
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Dark Matter ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Viral Pathogens ◽  
Antiviral Immune Response ◽  
Cellular Immune ◽  
Antiviral Gene

Long disregarded as junk DNA or genomic dark matter, endogenous retroviruses (ERVs) turned out to represent important components of the antiviral immune response. These remnants of once-infectious retroviruses not only regulate cellular immune activation, but may even directly target invading viral pathogens. In this review, we summarize mechanisms, by which retroviral fossils protect us from viral infections. One focus will be on recent advances in the role of ERVs as regulators of antiviral gene expression.

scholarly journals The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood

2021 ◽  
Vol 12 ◽  
Author(s):  
Ephraim L. Tsalik ◽  
Cassandra Fiorino ◽  
Ammara Aqeel ◽  
Yiling Liu ◽  
Ricardo Henao ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Immune Response ◽  
Host Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Wide Spectrum ◽  
Transcriptional Response ◽  
Myeloid Cell ◽  
Down Regulation

Viruses cause a wide spectrum of clinical disease, the majority being acute respiratory infections (ARI). In most cases, ARI symptoms are similar for different viruses although severity can be variable. The objective of this study was to understand the shared and unique elements of the host transcriptional response to different viral pathogens. We identified 162 subjects in the US and Sri Lanka with infections due to influenza, enterovirus/rhinovirus, human metapneumovirus, dengue virus, cytomegalovirus, Epstein Barr Virus, or adenovirus. Our dataset allowed us to identify common pathways at the molecular level as well as virus-specific differences in the host immune response. Conserved elements of the host response to these viral infections highlighted the importance of interferon pathway activation. However, the magnitude of the responses varied between pathogens. We also identified virus-specific responses to influenza, enterovirus/rhinovirus, and dengue infections. Influenza-specific differentially expressed genes (DEG) revealed up-regulation of pathways related to viral defense and down-regulation of pathways related to T cell and neutrophil responses. Functional analysis of entero/rhinovirus-specific DEGs revealed up-regulation of pathways for neutrophil activation, negative regulation of immune response, and p38MAPK cascade and down-regulation of virus defenses and complement activation. Functional analysis of dengue-specific up-regulated DEGs showed enrichment of pathways for DNA replication and cell division whereas down-regulated DEGs were mainly associated with erythrocyte and myeloid cell homeostasis, reactive oxygen and peroxide metabolic processes. In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections.

scholarly journals How dendritic cells sense and respond to viral infections

2021 ◽  
Vol 135 (19) ◽  
pp. 2217-2242
Author(s):  
Laura Marongiu ◽  
Mihai Valache ◽  
Fabio A. Facchini ◽  
Francesca Granucci
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Type I Interferons ◽  
Type I ◽  
Viral Pathogens ◽  
Cross Presentation ◽  
Antiviral Responses ◽  
Sense And Respond

Abstract The ability of dendritic cells (DCs) to sense viral pathogens and orchestrate a proper immune response makes them one of the key players in antiviral immunity. Different DC subsets have complementing functions during viral infections, some specialize in antigen presentation and cross-presentation and others in the production of cytokines with antiviral activity, such as type I interferons. In this review, we summarize the latest updates concerning the role of DCs in viral infections, with particular focus on the complex interplay between DC subsets and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Despite being initiated by a vast array of immune receptors, DC-mediated antiviral responses often converge towards the same endpoint, that is the production of proinflammatory cytokines and the activation of an adaptive immune response. Nonetheless, the inherent migratory properties of DCs make them a double-edged sword and often viral recognition by DCs results in further viral dissemination. Here we illustrate these various aspects of the antiviral functions of DCs and also provide a brief overview of novel antiviral vaccination strategies based on DCs targeting.

scholarly journals Learning from Bats to Escape from Potent or Severe Viral Infections

2021 ◽  
Author(s):  
Vijay Kumar
Keyword(s):  
Immune Response ◽  
Crucial Role ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Severe Infection ◽  
Viral Pathogens ◽  
Adaptive Immune ◽  
Serious Infections ◽  
Animal Reservoirs

The COVID-19 pandemic that started in December 2019 in Wuhan city, China has created chaos all over the world with over 185 million infection cases and 4 million deaths world-wide. The pathogen behind COVID-19 has been identified as severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) that is more close to the previous SARS-CoV responsible for SARS epidemic 2002–2003. Although, SARS-CoV-2 also differs from SARS-CoV in many aspects as indicated by genetic studies. For example, SARS-CoV does not have a furin binding domain or site, whereas its presence in SARS-CoV-2 spike (S) protein increases its potential for infectivity. The horseshoe bats (Rhinolphus species) from China are considered as primary animal reservoirs for SARS-CoV and SARS-CoV-2. However, along with CoVs, bats also harbor many other viral pathogens (Ebola, Nipah, and Hendra viruses) without having serious infections. The bat physiology plays a crucial role in harboring these viruses along with adaptations to longevity and slow aging process. The immune system plays a crucial role in the clearance or establishment of the infection. Present chapter discusses different immunological aspects (innate immune response comprising the virus recognizing pattern recognition receptors (PRRs), type 1 interferon production, pro- and anti-inflammatory immune response, and adaptive immune response) that help bats to control viral infection without getting a severe infection as compared to other mammals, including humans.

The Diagnosis of Viral Disease by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 270-273
Author(s):  
William B. McCombs ◽  
Cameron E. McCoy
Keyword(s):  
Electron Microscopy ◽  
Hospital Stay ◽  
Viral Infections ◽  
Medical Profession ◽  
Bacterial Pathogens ◽  
Viral Disease ◽  
Viral Pathogens ◽  
Academic Interest ◽  
The Past

Recent years have brought a reversal in the attitude of the medical profession toward the diagnosis of viral infections. Identification of bacterial pathogens was formerly thought to be faster than identification of viral pathogens. Viral identification was dismissed as being of academic interest or for confirming the presence of an epidemic, because the patient would recover or die before this could be accomplished. In the past 10 years, the goal of virologists has been to present the clinician with a viral identification in a matter of hours. This fast diagnosis has the potential for shortening the patient's hospital stay and preventing the administering of toxic and/or expensive antibiotics of no benefit to the patient.

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