scholarly journals Distinct Molecular Mechanisms of Host Immune Response Modulation by Arenavirus NP and Z Proteins

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 784
Author(s):  
Robert J. Stott ◽  
Thomas Strecker ◽  
Toshana L. Foster
Keyword(s):  
Immune Responses ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Significant Risk ◽  
Host Protein ◽  
Response Modulation ◽  
Species Barrier ◽  
African Countries ◽  
Host Immune Responses ◽  
Cellular Pathways

Endemic to West Africa and South America, mammalian arenaviruses can cross the species barrier from their natural rodent hosts to humans, resulting in illnesses ranging from mild flu-like syndromes to severe and fatal haemorrhagic zoonoses. The increased frequency of outbreaks and associated high fatality rates of the most prevalent arenavirus, Lassa, in West African countries, highlights the significant risk to public health and to the socio-economic development of affected countries. The devastating impact of these viruses is further exacerbated by the lack of approved vaccines and effective treatments. Differential immune responses to arenavirus infections that can lead to either clearance or rapid, widespread and uncontrolled viral dissemination are modulated by the arenavirus multifunctional proteins, NP and Z. These two proteins control the antiviral response to infection by targeting multiple cellular pathways; and thus, represent attractive targets for antiviral development to counteract infection. The interplay between the host immune responses and viral replication is a key determinant of virus pathogenicity and disease outcome. In this review, we examine the current understanding of host immune defenses against arenavirus infections and summarise the host protein interactions of NP and Z and the mechanisms that govern immune evasion strategies.

scholarly journals Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

2016 ◽  
Vol 90 (8) ◽  
pp. 3810-3818 ◽  
Author(s):  
Bjoern Meyer ◽  
Hinh Ly
Keyword(s):  
Immune Responses ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Multiorgan Failure ◽  
Hemorrhagic Fever ◽  
Innate Immune ◽  
Lassa Virus ◽  
Immune Recognition ◽  
African Countries ◽  
Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

scholarly journals MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

2021 ◽  
Vol 11 (6) ◽  
pp. 564
Author(s):  
Chin-Man Wang ◽  
Keng-Poo Tan ◽  
Yeong-Jian Jan Wu ◽  
Jing-Chi Lin ◽  
Jian-Wen Zheng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Healthy Controls ◽  
Hla B27 ◽  
Host Immune Responses ◽  
Histocompatibility Complex ◽  
High Level ◽  
Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

Molecular Mechanisms of Host Immune Responses to Entamoeba

2021 ◽  
pp. 461-477
Author(s):  
Moisés Martínez-Castillo ◽  
Jesús Serrano-Luna ◽  
Daniel Coronado-Velázquez ◽  
Judith Pacheco-Yépez ◽  
Mireya de la Garza ◽  
...  
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Host Immune Responses

Nutritional control of gastrointestinal parasitism in lactating rats

2005 ◽  
Vol 2005 ◽  
pp. 11-11 ◽  
Author(s):  
J.G.M. Houdijk ◽  
N.S. Jessop ◽  
D.P. Knox ◽  
I. Kyriazakis
Keyword(s):  
Immune Responses ◽  
Indirect Evidence ◽  
Host Protein ◽  
Nippostrongylus Brasiliensis ◽  
Host Immune Responses ◽  
Protein Nutrition ◽  
Intestinal Nematode ◽  
Nematode Parasites ◽  
Periparturient Period ◽  
Protein Supply

Small ruminant studies have shown that a reduction in protein scarcity, through either an increase in protein supply or reduction in protein demand, results in reduced nematode egg excretion and worm burdens during the periparturient period (Houdijk and Athanasiadou, 2003). Whilst this reduced degree of parasitism indirectly suggests that such nutritional effects are mediated through changes in host immune responses, there is only limited direct evidence for this. A rodent model may be used for directly assessing immune responses that underlie nutritional control of nematode parasites. There is indirect evidence that lactating rats undergo a breakdown of immunity to the intestinal nematode Nippostrongylus brasiliensis (Houdijk et al., 2003). Provided that this breakdown is sensitive to protein nutrition, this model may be used for elucidating interactions between nutrition and immunity to parasites. Therefore, we assessed whether breakdown of immunity to N. brasiliensis in the lactating rat is sensitive to host protein nutrition.

scholarly journals Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 729
Author(s):  
Bo Yang ◽  
Xiaohui Zhang ◽  
Dajun Zhang ◽  
Jing Hou ◽  
GuoWei Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Immune Responses ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Vesicular Disease

Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses.

scholarly journals Probing the Unknowns in Cytokinin-Mediated Immune Defense in Arabidopsis with Systems Biology Approaches

2014 ◽  
Vol 8 ◽  
pp. BBI.S13462 ◽  
Author(s):  
Muhammad Naseem ◽  
Meik Kunz ◽  
Thomas Dandekar
Keyword(s):  
Systems Biology ◽  
Immune Responses ◽  
Protein Interactions ◽  
Immune Defense ◽  
Immune Functions ◽  
Protein Protein Interactions ◽  
Cytokinin Signaling ◽  
Host Immune Responses ◽  
Arabidopsis Protein ◽  
Underlying Mechanisms

Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein—protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.

scholarly journals Comparative multiplexed interactomics of SARS-CoV-2 and homologous coronavirus non-structural proteins identifies unique and shared host-cell dependencies

2020 ◽  
Author(s):  
Jonathan P. Davies ◽  
Katherine M. Almasy ◽  
Eli F. McDonald ◽  
Lars Plate
Keyword(s):  
Host Cell ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Sequence Similarity ◽  
Host Protein ◽  
Structural Proteins ◽  
Cell Protein ◽  
High Sequence Similarity ◽  
Innate Immune Signaling ◽  
Human Coronaviruses

ABSTRACTHuman coronaviruses (hCoV) have become a threat to global health and society, as evident from the SARS outbreak in 2002 caused by SARS-CoV-1 and the most recent COVID-19 pandemic caused by SARS-CoV-2. Despite high sequence similarity between SARS-CoV-1 and −2, each strain has distinctive virulence. A better understanding of the basic molecular mechanisms mediating changes in virulence is needed. Here, we profile the virus-host protein-protein interactions of two hCoV non-structural proteins (nsps) that are critical for virus replication. We use tandem mass tag-multiplexed quantitative proteomics to sensitively compare and contrast the interactomes of nsp2 and nsp4 from three betacoronavirus strains: SARS-CoV-1, SARS-CoV-2, and hCoV-OC43 – an endemic strain associated with the common cold. This approach enables the identification of both unique and shared host cell protein binding partners and the ability to further compare the enrichment of common interactions across homologs from related strains. We identify common nsp2 interactors involved in endoplasmic reticulum (ER) Ca2+ signaling and mitochondria biogenesis. We also identifiy nsp4 interactors unique to each strain, such as E3 ubiquitin ligase complexes for SARS-CoV-1 and ER homeostasis factors for SARS-CoV-2. Common nsp4 interactors include N-linked glycosylation machinery, unfolded protein response (UPR) associated proteins, and anti-viral innate immune signaling factors. Both nsp2 and nsp4 interactors are strongly enriched in proteins localized at mitochondrial-associated ER membranes suggesting a new functional role for modulating host processes, such as calcium homeostasis, at these organelle contact sites. Our results shed light on the role these hCoV proteins play in the infection cycle, as well as host factors that may mediate the divergent pathogenesis of OC43 from SARS strains. Our mass spectrometry workflow enables rapid and robust comparisons of multiple bait proteins, which can be applied to additional viral proteins. Furthermore, the identified common interactions may present new targets for exploration by host-directed anti-viral therapeutics.

scholarly journals Identification of viral-mediated pathogenic mechanisms in neurodegenerative diseases using network-based approaches

2020 ◽  
Author(s):  
Anna Onisiforou ◽  
George M. Spyrou
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Interactions ◽  
Symptomatic Relief ◽  
Critical Role ◽  
Unmet Need ◽  
Host Protein ◽  
Human Interactome ◽  
Pathogenic Mechanisms ◽  
Host Immune Responses ◽  
Kegg Pathways

AbstractDuring the course of a viral infection, virus-host protein-protein interactions (PPIs) play a critical role in allowing viruses to evade host immune responses, replicate and hence survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various complex diseases, from cancer to neurodegenerative diseases (NDs). There are evidences suggesting that viral-mediated perturbations are a possible pathogenic aetiology in several NDs such as Amyloid Later Sclerosis, Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis (MS), as they can cause degeneration of neurons via both direct and/or indirect actions. These diseases share several common pathological mechanisms, as well as unique disease mechanisms that reflect disease phenotype. NDs are chronic degenerative diseases of the central nervous system and current therapeutic approaches provide only mild symptomatic relief rather than treating the disease at heart, therefore there is unmet need for the discovery of novel therapeutic targets and pharmacotherapies. In this paper we initially review databases and tools that can be utilized to investigate viral-mediated perturbations in complex NDs using network-based analysis by examining the interaction between the ND-related PPI disease networks and the virus-host PPI network. Afterwards we present our integrative network-based bioinformatics approach that accounts for pathogen-genes-disease related PPIs with the aim to identify viral-mediated pathogenic mechanisms focusing in MS disease. We identified 7 high centrality nodes that can act as disease communicator nodes and exert systemic effects in the MS enriched KEGG pathways network. In addition, we identified 12 KEGG pathways targeted by 67 viral proteins from 8 viral species that might exert viral-mediated pathogenic mechanisms in MS by interacting with the disease communicator nodes. Finally, our analysis highlighted the Th17 differentiation pathway, a hub-bottleneck disease communicator node and part of the 12 underlined KEGG pathways, as a key viral-mediated pathogenic mechanism and a possible therapeutic target for MS disease.

scholarly journals Innate Immunity Modulating Impurities and the Immunotoxicity of Nanobiotechnology-Based Drug Products

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7308
Author(s):  
Claire K. Holley ◽  
Marina A. Dobrovolskaia
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Pharmaceutical Products ◽  
Drug Effectiveness ◽  
Host Immune Responses ◽  
Drug Products ◽  
The Many

Innate immunity can be triggered by the presence of microbial antigens and other contaminants inadvertently introduced during the manufacture and purification of bionanopharmaceutical products. Activation of these innate immune responses, including cytokine secretion, complement, and immune cell activation, can result in unexpected and undesirable host immune responses. These innate modulators can also potentially stimulate the activation of adaptive immune responses, including the formation of anti-drug antibodies which can impact drug effectiveness. To prevent induction of these adverse responses, it is important to detect and quantify levels of these innate immunity modulating impurities (IIMIs) that may be present in drug products. However, while it is universally agreed that removal of IIMIs from drug products is crucial for patient safety and to prevent long-term immunogenicity, there is no single assay capable of directly detecting all potential IIMIs or indirectly quantifying downstream biomarkers. Additionally, there is a lack of agreement as to which of the many analytical assays currently employed should be standardized for general IIMI screening. Herein, we review the available literature to highlight cellular and molecular mechanisms underlying IIMI-mediated inflammation and its relevance to the safety and efficacy of pharmaceutical products. We further discuss methodologies used for direct and indirect IIMI identification and quantification.

scholarly journals Arms and ammunitions: effectors at the interface of rice and it’s pathogens and pests

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sohini Deb ◽  
Vishnu Narayanan Madhavan ◽  
C. G. Gokulan ◽  
Hitendra K. Patel ◽  
Ramesh V. Sonti
Keyword(s):  
Immune Responses ◽  
Protein Interactions ◽  
Target Genes ◽  
Plant Cells ◽  
Effector Proteins ◽  
Protein Protein Interactions ◽  
Cellular Machinery ◽  
Rice Pathogens ◽  
Cellular Pathways ◽  
Major Pathogens

AbstractThe plant immune system has evolved to resist attack by pathogens and pests. However, successful phytopathogens deliver effector proteins into plant cells where they hijack the host cellular machinery to suppress the plant immune responses and promote infection. This manipulation of the host cellular pathways is done by the pathogen using various enzymatic activities, protein- DNA or protein- protein interactions. Rice is one the major economically important crops and its yield is affected by several pathogens and pests. In this review, we summarize the various effectors at the plant- pathogen/ pest interface for the major pathogens and pests of rice, specifically, on the mode of action and target genes of the effector proteins. We then compare this across the major rice pathogens and pests in a bid to understand probable conserved pathways which are under attack from pathogens and pests in rice. This analysis highlights conserved patterns of effector action, as well as unique host pathways targeted by the pathogens and pests.

Sign in / Sign up

Export Citation Format

Share Document