Herpes Simplex Virus Vaccines and the Viral Strategies Used to Evade Host Immunity
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
gC is expressed on both the virion envelope, as well as on the surface of virus-infected cells. gC of both HSV-1 and HSV-2 binds C3b when in a purified form and when expressed on the surface of transfected cells (48,49). Regions of the gC proteins that are involved in C3b binding are well conserved in both proteins. Four regions on gC-1 and three regions on gC-2 are known to be important (50,51). Binding of gC-1 to C3b inhibits activation of the classical pathway on the HSV-1 virion, and may function in a similar manner for gC-2 (49,52). Differences do exist however, as gC-1, but not gC-2, is able to accelerate the decay of the alternative pathway C3 convertase, C3bBb, preventing lysis of HSV-infected cells (49,53). Properdin extends the lifetime of C3bBb three- or four-fold by binding to and stabilizing the C3bBb complex. This extended lifetime should increase the amount of C3b functioning as a component of the alternative C3 convertase, thereby amplifying the complement cascade, as well as the amount of C3b coating the cell surface. gC-1 destabilizes the C3 convertase by inhibiting the binding of properdin to C3b, which limits the effectiveness of the alternative complement pathway in lysing HSV-infected cells (43,50). gC-1 has also been shown to inhibit the interaction of C5 with C3b, leading to the disruption of both the classical and alternative complement activation pathways at the level of the C5 convertase (53). Expression of gC-1 may therefore limit the assembly of the MAC on membranes of HSV virions and infected cells.
Clinical Toxicology of Snakebite In Africa and The Middle East / Arabian Peninsula
Jürg Meier, Julian White in Handbook of: Clinical Toxicology of Animal Venoms and Poisons, 2017
The venoms of the dangerous African colubrids, D. typus and Thelotornis sp., have low intravenous mouse median lethal doses (LD50) of 0.07 and 1.23 mg/kg respectively. Both venoms contain enzymes which activate prothrombin and possibly Factor X which explains the disseminated intravascular coagulation with deposition of microthrombi observed in human victims of envenoming. A human victim of D. typus showed activation of the alternative complement pathway. The venoms of a number of other African colubrid snakes such as the Natal green snake (Philothamnus natalensis) demonstrate powerful procoagulant activity which, in unusual circumstances, might prove clinically significant. Nothing is known about the venoms of Malpolon species.
The complement system in health and disease
Gabriel Virella in Medical Immunology, 2019
The biological significance of the alternative pathway can be understood if we consider, as an example, an infection with a hypothetical bacterium. Since all normal individuals have low levels of antibody to most bacteria, some limited classical pathway activation occurs. Theoretically, in the presence of large numbers of bacteria, the relatively low levels of specific antibody may be effectively absorbed by antigens present on the proliferating bacteria, allowing uncoated bacteria to escape destruction by the more effective classical pathway. While optimal classical pathway function is awaiting production of large amounts of specific antibody, C3b molecules (produced via normal C3 turnover) are slowly (inadvertently) deposited on the bacteria, initiating the alternative complement sequence. Most bacteria, fungi, and viruses will activate the alternative pathway, but with varying efficiencies. That is, there is a large variability in the avidity and degree of the interaction with this pathway, depending on the species and strain of microorganism. Perhaps aiding the activation of the alternative pathway are the proteolytic enzymes being produced by microorganisms, which directly activate components like C3. If a higher rate of C3 conversion to C3b and C3a occurs near the membrane of the organism, C3b molecules will more rapidly deposit on the foreign surface via their highly reactive C3b binding site, and the alternative complement pathway will be more effectively initiated. On another note, large levels of powerful broad-spectrum proteases located on bacterial surfaces could protect the bacteria from the effects of complement by simply degrading the complement components as they deposit.
Acute renal failure with need for renal replacement therapy as a complication of zoonotic S. zooepidemicus infection: case report and review of the literature
Published in Acta Clinica Belgica, 2018
Laurens Veldeman, Katrien De Wilde, Dirk Vogelaers, Evelyne Lerut, An Vonck, Dien Mertens, Annelies Koch, Jan Beckers
A renal biopsy is not indicated in children with a typical course of PSGN unless the diagnosis is doubtful, or in the face of rapidly progressive renal insufficiency.1 Histopathology shows a light microscopic pattern of acute exudative glomerulonephritis with diffuse endocapillary proliferation and infiltration of different immunocompetent cells (mainly neutrophils, but also macrophages and T-lymphocyts).4,11 Typical immunofluorescence shows mostly granular C3 and IgG glomerular staining in mesangium and basement membrane (a ‘starry sky’ pattern).12 Subepithelial electron dense depositions, ‘humps’, are seen on electron microscopy, (with or without intramembranous, mesangial, and subendothelial deposits).11 These immune depositions are shown to consist of IgG, C3, properdin, and C5, components of the alternative complement pathway, and never consist of classical complement pathway components such as C1q or C4. This observation led to the hypothesis that the alternative complement pathway is essential in disease activity.1,13,14
C3 glomerulopathy: experience of a pediatric nephrology center
Published in Acta Clinica Belgica, 2021
Fatma Yazılıtaş, Evrim Kargın Çakıcı, Eda Didem Kurt Şükür, Gökçe Can, Tülin Güngör, Diclehan Orhan, Mehmet Bülbül
We observed that the most common finding in kidney biopsy was mesangial and/or membranoproliferative pattern. Our immunofluorescence studies showed the hallmark of bright glomerular C3 staining in all biopsies. There was no accumulation of classical complement pathway factors such as C1, C2, or C4 in our patients, except one patient who was treated with eculizumab in the present study. It may be explained by the fact that the alternative complement pathway on one’s own may not reflect disease activity. Our results of both immunohistochemistry studies and kidney biopsy were consistent with other studies [11,14,15]. C3G is categorized into its two subtypes as DDD and C3GN by electron microscopy. Unfortunately, most of the patients did not have an electron microscopic examination in our study.
Association of Systemic Inflammatory Factors with Progression to Advanced Age-related Macular Degeneration
Published in Ophthalmic Epidemiology, 2022
Brandie D. Wagner, Jennifer L. Patnaik, Alan G. Palestine, Ashley A. Frazer-Abel, Rebecca Baldermann, V. Michael Holers, Marc T. Mathias, Naresh Mandava, Anne M. Lynch
Established risk factors for AMD progression include: age,7 gender, cigarette smoking,8,9 body mass index10 presence of cardiovascular disease, AMD status of the fellow eye,9 diet11,12 number of drusen deposits, and genetic variants.13,14 AMD is also linked with local inflammatory events15–20 and genetic variants of complement factors that promote activation, specifically in the complement factor H gene which increase activity of the alternative pathway of complement activation and the amplification loop.21–23 Apart from a small number of studies in advanced AMD,24–31 including one from our group,32 the significance of systemic inflammation in AMD, and specifically in iAMD, has not been fully addressed. Moreover, these studies have primarily focused on activation of the alternative complement pathway, although activation of the innate immune system comprises multiple inflammatory pathways which interact in a complex manner. In a recent study of the complement system in patients with iAMD, levels of several complement factors, involved in both the classical and alternative pathways, were significantly altered in the iAMD cases versus controls with no AMD.33 Additionally, a recent proteomic study from our group also suggested an important role of systemic inflammation extrinsic to the alternative complement pathway in iAMD.34
Related Knowledge Centers
- Complement Factor B
- Complement Receptor 1
- Innate Immune System
- Opsonin
- Complement System
- Cascade Reaction
- Factor D
- C3-Convertase
- Properdin
- Complement Membrane Attack Complex