Complement Evasion Strategies of Viruses: An Overview

Agrawal, Palak; Renuka, Nawadkar; Ojha, Hina; Kumar, Jitendra; Sahu, Arvind

doi:10.3389/fmicb.2017.01117

Cited by 129 publications

(140 citation statements)

References 230 publications

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“…[47][48][49] There are, however, potential complications from the expression of hCRPs, such as susceptibility to human infectious agents. Human complement regulators are used by many pathogens as co-receptors to enter host cells 42 and evade host immunity, 50,51 or as a receptor of toxins produced by the pathogens. 52 There is, therefore, the potential that a pig expressing one or more hCRPs might be at a higher risk for infection, particularly of the graft itself, though there do not appear to be any reports in this respect in preclinical models.…”

Section: E Xpre Ss I On Of H Uman Complement-reg Ul Atory Proteinsmentioning

confidence: 99%

Justification of specific genetic modifications in pigs for clinical organ xenotransplantation

Cooper

Hara

Iwase

et al. 2019

Xenotransplantation

129

131

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Xenotransplantation research has made considerable progress in recent years, largely through the increasing availability of pigs with multiple genetic modifications. We suggest that a pig with nine genetic modifications (ie, currently available) will provide organs (initially kidneys and hearts) that would function for a clinically valuable period of time, for example, >12 months, after transplantation into patients with end‐stage organ failure. The national regulatory authorities, however, will likely require evidence, based on in vitro and/or in vivo experimental data, to justify the inclusion of each individual genetic modification in the pig. We provide data both from our own experience and that of others on the advantages of pigs in which (a) all three known carbohydrate xenoantigens have been deleted (triple‐knockout pigs), (b) two human complement‐regulatory proteins (CD46, CD55) and two human coagulation‐regulatory proteins (thrombomodulin, endothelial cell protein C receptor) are expressed, (c) the anti‐apoptotic and “anti‐inflammatory” molecule, human hemeoxygenase‐1 is expressed, and (d) human CD47 is expressed to suppress elements of the macrophage and T‐cell responses. Although many alternative genetic modifications could be made to an organ‐source pig, we suggest that the genetic manipulations we identify above will all contribute to the success of the initial clinical pig kidney or heart transplants, and that the beneficial contribution of each individual manipulation is supported by considerable experimental evidence.

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Section: E Xpre Ss I On Of H Uman Complement-reg Ul Atory Proteinsmentioning

confidence: 99%

Justification of specific genetic modifications in pigs for clinical organ xenotransplantation

Cooper

Hara

Iwase

et al. 2019

Xenotransplantation

129

131

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“…However, human complement regulators are used by many pathogens as co‐receptors to enter host cells and evade host immunity (Table ), or as a receptor of toxins produced by the pathogens . There is, therefore, the potential that a pig expressing one or more human complement regulators might be at a higher risk for infection, particularly of the graft itself.…”

Section: Complement Activation In Xenotransplantationmentioning

confidence: 99%

The complex functioning of the complement system in xenotransplantation

Zhou

Hara

Cooper

2019

Xenotransplantation

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The role of complement in xenotransplantation is well-known, and is a topic that has been reviewed previously. However, our understanding of the immense complexity of its interaction with other constituents of the innate immune response and of the coagulation, adaptive immune, and inflammatory responses to a xenograft is steadily increasing. In addition, the complement system plays a function in metabolism and homeostasis. New reviews at intervals are therefore clearly warranted. The pathways of complement activation, the function of the complement system, and the interaction between complement and coagulation, inflammation, and the adaptive immune system in relation to xenotransplantation are reviewed. Through several different mechanisms, complement activation is a major factor in contributing to xenograft failure. In the organ-source pig, the detrimental influence of the complement system is seen during organ harvest and preservation, e.g., in ischemia-reperfusion injury. In the recipient, the effect of complement can be seen through its interaction with the immune, coagulation, and inflammatory responses. Genetic-engineering and other therapeutic methods by which the xenograft can be protected from the effects of complement activation are discussed. The review provides an updated source of reference to this increasingly complex subject.

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“…The complement system is an important branch of innate immunity that plays an essential role in the clearance of pathogens. The complement system is triggered by three main pathways, the classical, the lectin, and the alternative pathways [77]. The first two pathways are activated with the help of pattern recognition molecules, whereas the alternative pathway is activated spontaneously.…”

Section: Innate Immunity In Iav Infectionsmentioning

confidence: 99%

“…Complexes activated after the classical and lectin pathways, cleave C4 and C2, resulting in the generation of C4bC2a (C3 convertase). In the alternative pathway, spontaneous hydrolysis of native C3 results in the formation of C3b-like C3 that binds factor B and after cleavage by factor D forms the initial C3 convertase [77]. The three pathways converge at the cleavage of C3 into C3a and C3b by C3 convertases (C4b, 2a and C3b, Bb).…”

Section: Innate Immunity In Iav Infectionsmentioning

confidence: 99%

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Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Nogales¹,

DeDiego

2019

Pathogens

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A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness. multiple mechanisms, although there are some differences between strains. For that genome plasticity, IAV take advantage of multiple strategies, such as alternative splicing, frameshift mechanisms, and overlapping open reading frames (ORFs) [7][8][9]. In addition, the coding capability of the viral genome is extended by encoding multifunctional proteins that act at different steps during virus infection. of synthetized vRNP, ensuring that the vRNPs are available for packaging [24]. Moreover, NEP has also other functions during IAV infection, contributing to viral budding and to regulate viral RNA synthesis. NS1 is a multifunctional protein and a key viral factor that counteracts the host antiviral responses. NS1 has been shown to inhibit the production of interferon (IFN), the activity and expression of multiple interferon-induced genes (ISG) and the processing and nuclear transport of host mRNAs causing cellular shut-off [25,26]. Segment 3 of IAV also encodes two proteins, the polymerase component PA and PA-X. PA is translated directly from the PA mRNA, whereas PA-X is translated using a +1 frameshift mechanism from the same open reading frame (ORF) [9]. Synergistically with NS1, PA-X is also able to block the cellular antiviral responses by inhibiting host protein expression. Moreover, the PA-X protein has been shown to modulate host inflammation, immune responses, apoptosis, and virus pathogenesis [25][26][27][28][29][30].

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Complement Evasion Strategies of Viruses: An Overview

Cited by 129 publications

References 230 publications

Justification of specific genetic modifications in pigs for clinical organ xenotransplantation

Justification of specific genetic modifications in pigs for clinical organ xenotransplantation

The complex functioning of the complement system in xenotransplantation

Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

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