scholarly journals Recent advances in the understanding of trimeric autotransporter adhesins

2019 ◽  
Vol 209 (3) ◽  
pp. 233-242 ◽  
Author(s):  
Andreas R. Kiessling ◽  
Anchal Malik ◽  
Adrian Goldman
Keyword(s):  
Immune System ◽  
Infection Type ◽  
A Priori ◽  
Protein A ◽  
Initial Step ◽  
Infection Process ◽  
Secretion Systems ◽  
Specific Domain ◽  
Recent Advances ◽  
Type V

AbstractAdhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation.

scholarly journals Inborn errors of immunity—recent advances in research on the pathogenesis

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Motoi Yamashita ◽  
Kento Inoue ◽  
Tsubasa Okano ◽  
Tomohiro Morio
Keyword(s):  
Immune System ◽  
Hematopoietic Cell Transplantation ◽  
Epigenetic Modification ◽  
Genetic Disorder ◽  
Loss Of Function ◽  
Inborn Errors ◽  
Whole Genome Analysis ◽  
Curative Therapy ◽  
Inborn Errors Of Immunity ◽  
Recent Advances

AbstractPrimary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.

scholarly journals Intercellular Transmission of Naked Viruses through Extracellular Vesicles: Focus on Polyomaviruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1086
Author(s):  
Francois Helle ◽  
Lynda Handala ◽  
Marine Bentz ◽  
Gilles Duverlie ◽  
Etienne Brochot
Keyword(s):  
Immune System ◽  
Extracellular Vesicles ◽  
Rna Viruses ◽  
Viral Transmission ◽  
Viral Fitness ◽  
Host Cells ◽  
Dna Viruses ◽  
Recent Advances ◽  
Viral Particles ◽  
Similar Strategy

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

Recent Advances in Aptamers Targeting Immune System

Inflammation ◽  
2016 ◽  
Vol 40 (1) ◽  
pp. 295-302 ◽  
Author(s):  
Piao-Ping Hu
Keyword(s):  
Immune System ◽  
Recent Advances

Ontogeny of human mannan-binding protein, a lectin of the innate immune system

1995 ◽  
Vol 6 (1) ◽  
pp. 20-23 ◽  
Author(s):  
S. Thiel ◽  
T. Bjerke ◽  
D. Hansen ◽  
L. K. Poulsen ◽  
P. O. Schiøtz ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Binding Protein ◽  
Protein A ◽  
Innate Immune

A novel EP-involved pathway for iron release from soya bean seed ferritin

2010 ◽  
Vol 427 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Xiaoping Fu ◽  
Jianjun Deng ◽  
Haixia Yang ◽  
Taro Masuda ◽  
Fumiyuki Goto ◽  
...  
Keyword(s):  
Serine Protease ◽  
Protein A ◽  
Soya Bean ◽  
Iron Release ◽  
Bean Seed ◽  
Specific Domain ◽  
Exterior Surface ◽  
Legume Seeds ◽  
Seedling Germination ◽  
Ph Range

Iron in phytoferritin from legume seeds is required for seedling germination and early growth. However, the mechanism by which phytoferritin regulates its iron complement to these physiological processes remains unknown. In the present study, protein degradation is found to occur in purified SSF (soya bean seed ferritin) (consisting of H-1 and H-2 subunits) during storage, consistent with previous results that such degradation also occurs during seedling germination. In contrast, no degradation is observed with animal ferritin under identical conditions, suggesting that SSF autodegradation might be due to the EP (extension peptide) on the exterior surface of the protein, a specific domain found only in phytoferritin. Indeed, EP-deleted SSF becomes stable, confirming the above hypothesis. Further support comes from a protease activity assay showing that EP-1 (corresponding to the EP of the H-1 subunit) exhibits significant serine protease-like activity, whereas the activity of EP-2 (corresponding to the EP of the H-2 subunit) is much weaker. Consistent with the observation above, rH-1 (recombinant H-1 ferritin) is prone to degradation, whereas its analogue, rH-2, becomes very stable under identical conditions. This demonstrates that SSF degradation mainly originates from the serine protease-like activity of EP-1. Associated with EP degradation is a considerable increase in the rate of iron release from SSF induced by ascorbate in the amyloplast (pH range, 5.8–6.1). Thus phytoferritin may have facilitated the evolution of the specific domain to control its iron complement in response to cell iron need in the seedling stage.

scholarly journals Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression

2004 ◽  
Vol 85 (11) ◽  
pp. 3343-3351 ◽  
Author(s):  
Anna Zajakina ◽  
Tatyana Kozlovska ◽  
Ruta Bruvere ◽  
Jekaterina Aleksejeva ◽  
Paul Pumpens ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Semliki Forest Virus ◽  
Expression System ◽  
Protein A ◽  
Direct Repeat ◽  
Infection Process ◽  
Surface Proteins ◽  
B Virus ◽  
Internal Translation

Hepatitis B virus (HBV) pregenome RNA (pgRNA) serves as a translation template for the HBV core (HBc) protein and viral polymerase (Pol). HBV precore RNA (pcRNA) directs the synthesis of the precore (preC) protein, a precursor of the hepatitis B e antigen (HBeAg). pgRNA and pcRNA were expressed in the Semliki Forest virus (SFV) expression system. Besides the HBc and preC proteins, there was revealed the synthesis of all three forms of HBV surface (HBs) proteins: long (LHBs), middle (MHBs) and short (SHBs), the start codons of which are located more than 1000 nt downstream of the HBc and preC start codons. Moreover, other HBV templates, such as 3′-truncated pgRNA lacking 3′ direct repeat and Pol mRNA, both carrying internally the HBs sequences, provided the synthesis of three HBs protein forms in the SFV-driven expression system. Maximal production of the HBs was provided by Pol mRNA, while HBc- and preC-producing templates showed relatively low internal translation of the HBs. These data allow the proposal of a ribosome leaky scanning model of internal translation initiation for HBs proteins. The putative functional role of such exceptional synthesis of the HBs proteins from the pgRNA and pcRNA templates in the natural HBV infection process needs further evaluation.

Heterogeneous population dynamics of active particles: Progression, mutations, and selection dynamics

2017 ◽  
Vol 27 (04) ◽  
pp. 617-640 ◽  
Author(s):  
L. Gibelli ◽  
A. Ełaiw ◽  
M. A. Alghamdi ◽  
A. M. Althiabi
Keyword(s):  
Population Dynamics ◽  
Immune System ◽  
Virus Infection ◽  
Mathematical Structure ◽  
Infection Process ◽  
Heterogeneous Population ◽  
Cellular Aging ◽  
Active Particles ◽  
Selection Dynamics ◽  
Classical Models

This paper proposes a conceptual revisiting of population dynamics to include heterogeneous behaviors of individuals, mutations, and selection. The first part of the paper focuses on the derivation of a general mathematical structure which permits to describe systems composed of individuals whose interactions are stochastic. Hybrid models where some of the populations follow a deterministic dynamics are also discussed. The second part deals with two specific applications, namely the effect of the cellular aging in the virus infection process and the dynamics of virus mutation and competition with the immune system. Sample simulations are presented and classical models of population dynamics are critically analyzed in light of the proposed approach.

scholarly journals Recent advances in understanding HIV evolution

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 597 ◽  
Author(s):  
Sophie M. Andrews ◽  
Sarah Rowland-Jones
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune System ◽  
Reverse Transcriptase ◽  
Viral Diversity ◽  
Recent Advances ◽  
Technological Advances ◽  
Generation Times ◽  
Immunodeficiency Virus ◽  
Shed Light ◽  
Hiv Evolution

The human immunodeficiency virus (HIV) evolves rapidly owing to the combined activity of error-prone reverse transcriptase, recombination, and short generation times, leading to extensive viral diversity both within and between hosts. This diversity is a major contributing factor in the failure of the immune system to eradicate the virus and has important implications for the development of suitable drugs and vaccines to combat infection. This review will discuss the recent technological advances that have shed light on HIV evolution and will summarise emerging concepts in this field.

scholarly journals Diversity of Functionally Distinct Clonal Sets of Human Conventional Memory B Cells That Bind Staphylococcal Protein A

2021 ◽  
Vol 12 ◽  
Author(s):  
Emily E. Radke ◽  
Zhi Li ◽  
David N. Hernandez ◽  
Hanane El Bannoudi ◽  
Sergei L. Kosakovsky Pond ◽  
...  
Keyword(s):  
Immune System ◽  
B Cells ◽  
B Cell ◽  
Binding Site ◽  
Protein A ◽  
Memory B Cells ◽  
Host Immune System ◽  
Staphylococcal Protein A ◽  
Staphylococcal Protein ◽  
Circulating Antibodies

Staphylococcus aureus, a common cause of serious and often fatal infections, is well-armed with secreted factors that disarm host immune defenses. Highly expressed in vivo during infection, Staphylococcal protein A (SpA) is reported to also contribute to nasal colonization that can be a prelude to invasive infection. Co-evolution with the host immune system has provided SpA with an Fc-antibody binding site, and a Fab-binding site responsible for non-immune superantigen interactions via germline-encoded surfaces expressed on many human BCRs. We wondered whether the recurrent exposures to S. aureus commonly experienced by adults, result in the accumulation of memory B-cell responses to other determinants on SpA. We therefore isolated SpA-specific class-switched memory B cells, and characterized their encoding VH : VL antibody genes. In SpA-reactive memory B cells, we confirmed a striking bias in usage for VH genes, which retain the surface that mediates the SpA-superantigen interaction. We postulate these interactions reflect co-evolution of the host immune system and SpA, which during infection results in immune recruitment of an extraordinarily high prevalence of B cells in the repertoire that subverts the augmentation of protective defenses. Herein, we provide the first evidence that human memory responses are supplemented by B-cell clones, and circulating-antibodies, that bind to SpA determinants independent of the non-immune Fc- and Fab-binding sites. In parallel, we demonstrate that healthy individuals, and patients recovering from S. aureus infection, both have circulating antibodies with these conventional binding specificities. These findings rationalize the potential utility of incorporating specially engineered SpA proteins into a protective vaccine.

scholarly journals Recent Advances in Zwitterionic Hydrogels: Preparation, Property, and Biomedical Application

Gels ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 46
Author(s):  
Sihang Liu ◽  
Jingyi Tang ◽  
Fangqin Ji ◽  
Weifeng Lin ◽  
Shengfu Chen
Keyword(s):  
Immune System ◽  
Polyethylene Glycol ◽  
Biomedical Applications ◽  
Biomedical Application ◽  
Synthetic Polymers ◽  
Human Environment ◽  
The Past ◽  
Recent Advances ◽  
Nonspecific Protein Adsorption ◽  
Anionic Groups

Nonspecific protein adsorption impedes the sustainability of materials in biologically related applications. Such adsorption activates the immune system by quick identification of allogeneic materials and triggers a rejection, resulting in the rapid failure of implant materials and drugs. Antifouling materials have been rapidly developed in the past 20 years, from natural polysaccharides (such as dextran) to synthetic polymers (such as polyethylene glycol, PEG). However, recent studies have shown that traditional antifouling materials, including PEG, still fail to overcome the challenges of a complex human environment. Zwitterionic materials are a class of materials that contain both cationic and anionic groups, with their overall charge being neutral. Compared with PEG materials, zwitterionic materials have much stronger hydration, which is considered the most important factor for antifouling. Among zwitterionic materials, zwitterionic hydrogels have excellent structural stability and controllable regulation capabilities for various biomedical scenarios. Here, we first describe the mechanism and structure of zwitterionic materials. Following the preparation and property of zwitterionic hydrogels, recent advances in zwitterionic hydrogels in various biomedical applications are reviewed.

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