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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The conjugated MS2 VLPs were used to study parvovirus B19, which has an extraordinary narrow tissue tropism, showing only productive infection in erythroid precursor cells in the bone marrow. The VP1u, a unique region of viral protein 1 that mediated the B19 uptake into cells of the erythroid lineage, was chemically coupled to the MS2 capsid and tested for the internalization capacity on permissive cells (Leisi et al. 2016). The MS2-VP1u bioconjugate mimicked the specific internalization of the native B19 into erythroid precursor cells, which further coincided with the restricted infection profile.
Autoimmunity and Immune Pathological Aspects of Virus Disease
Published in Irun R. Cohen, Perspectives on Autoimmunity, 2020
H. Wege, R. Dörries, P. Massa, R. Watanabe
Some detailed information is available on animal diseases of this type. The virus causing equine infectious anemia (EIA) is a retrovirus similar to visna (Section II.B.4) which induces an acute disease in horses.98-100 Surviving animals can, after months to years, develop a recurrent disease associated with anemia, lesions of lymph organs, hypergammaglobulinemia, hepatitis, and glomerulonephritis. High titers of antiviral antibodies do not hinder viremia. Infectious immune complexes consist of virus antigen, immunoglobulin, and complement C3. Macrophages are the central source for replication of virus and spread to different organs. Infectious immune complexes are readily taken up by phagocytes. Binding of antibodies to viral antigen displayed on the surface of erythrocytes induces the complement cascade leading to lysis of these cells. The episodic recurrence of clinical disease might be due to antigenic changes of the virus during persistency in less permissive cells (by integration of proviral DNA) giving rise to variants which escape neutralization.
Antiviral Treatment
Published in Marie Studahl, Paola Cinque, Tomas Bergström, Herpes Simplex Viruses, 2017
Sensitivity/susceptibility of HSV to antiviral drugs is measured by PR, DU, CPE, or AS-Assays. Briefly, permissive cells are infected with a diluted viral inoculum in the presence of an antiviral agent. With a light microscope, the number of plaques and the extent of cytophatic effects or stained cells are analyzed after an incubation period and the drug concentration that reduces viral plaques or CPE by 50% or 90% is determined (inhibitory concentration IC50 or IC90). More elegantly and broadly applicable, this method is performed with fluorescent dyes in anti-infective research and development (18,46). Resistance is defined by a breakpoint [e.g., multiples of the IC50 of the reference or set of wild-type strains, or simply IC50 (ACV)>2μg/mL (see above)]. Further refinements of the cell-based assay have been described in which virus DNA or viral antigens are used to determine the inhibitory effect; however, these techniques did not achieve widespread acceptance to date.
JC polyomavirus: a short review of its biology, its association with progressive multifocal leukoencephalopathy, and the diagnostic value of different methods to manifest its activity or presence
Published in Expert Review of Molecular Diagnostics, 2023
Carla Prezioso, Valeria Pietropaolo, Ugo Moens, Marco Ciotti
While there is no effective treatment for PML, in vitro and in vivo studies have proposed strategies in limiting this fatal disease. Because no specific and effective agents against HPyVs that have entered the clinics exist, intensive quests to alternative therapies are ongoing [153]. Specifically, an in vitro study involved gene editing using the CRISPR/Cas 9 system to target the JCPyV genome areas that serve as sites for the creation of guide RNAs for LTAg. This clever approach, which has proven effective in other viral infections, resulted in the suppression of viral replication in infected permissive cells and pointed to gene editing as a potential novel tool in the treatment of PML [154]. On the other end, in vivo studies targeting PD-1, a negative regulator of the immune system’s response that contributes to impaired viral clearance, reported that treatment of 8 PML patients with Pembrolizumab, an anti-PD-1 antibody, resulted in the activation of CD4+ and CD8+ activity, reduction of JCPyV viral load and clinical improvement or stabilization of the disease in five of them, although no significant change was observed in the remaining three [155]. These different results point out to immune checkpoint inhibitors as potential agents for PML treatment.
Accelerating HIV vaccine development using non-human primate models
Published in Expert Review of Vaccines, 2019
Mohammad Arif Rahman, Marjorie Robert-Guroff
In addition to neutralization-sensitive SIVsmE660, the other main SIV challenge viruses used in the field are SIVmac251, which has greater neutralization resistance, and SIVmac239, a clone of SIVmac251 which is highly neutralization resistant (Table 2) [75–77]. As SIVsm and SIVmac isolates are often used for heterologous challenges, the difference in neutralizability must be considered. The viruses are similar in tropism (CCR5), pathogenicity, and persistence of infection. Other parameters, however, introduce additional differences. A key factor is the species of permissive cells used for viral expansion in generating a challenge stock. Expansion on rhesus macaque cells is highly preferable to avoid introduction of human cellular components on virions which can be protective if vaccine immunogens also contain cellular components [78–80]. Efforts to improve challenge stocks are continually ongoing. Both the SIVsmE660 and SIVmac251 viruses were originally obtained from chronically infected animals. As transmitted/founder viruses that initiate infection have exhibited differences compared to viruses obtained during chronic infection [81,82], pathogenic transmitted/founder molecular clones from both viruses have been derived and may see use as challenge viruses [83]. These viruses not only will differ from current stocks, but also may exhibit differences depending on whether they are expanded by transfection or infection [84]. Transfected stocks have been reported to have lower virion-associated Env, and few and lower levels of cytokines and chemokines compared to infection stocks. In contrast, the infection-derived stocks have exhibited greater viral diversity.
The use of immunotherapy for the treatment of tuberculosis
Published in Expert Review of Respiratory Medicine, 2018
Octavio Ramos-Espinosa, León Islas-Weinstein, Marco Polo Peralta-Álvarez, Manuel Othoniel López-Torres, Rogelio Hernández-Pando
In a zebra fish model, reactive oxygen species induced cellular pathways regulated by TNFα and its interaction with eicosanoids determines the type of cell death [21]. In the model previously described, mycobacteria escaped microbicidal-resident macrophages by inducing the production of the chemokine CCL2 and the subsequent recruitment of a specific subpopulation of permissive monocytes that express the CCR2 receptor. These resident macrophages then transiently fused with the low-bactericidal monocytes aiding mycobacterial transference to these permissive cells and resulting in hematogenous bacterial spread [22].