scholarly journals Human Norovirus: Experimental Models of Infection

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 151 ◽  
Author(s):  
Kyle Todd ◽  
Ralph Tripp

Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. HuNoV infections lead to substantial societal and economic burdens. There are currently no licensed vaccines or therapeutics for the prevention or treatment of HuNoVs. A lack of well-characterized in vitro and in vivo infection models has limited the development of HuNoV countermeasures. Experimental infection of human volunteers and the use of related viruses such as murine NoV have provided helpful insights into HuNoV biology and vaccine and therapeutic development. There remains a need for robust animal models and reverse genetic systems to further HuNoV research. This review summarizes available HuNoV animal models and reverse genetic systems, while providing insight into their usefulness for vaccine and therapeutic development.

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 19-22
Author(s):  
Marcel B. Roberfroid ◽  
Fabienne Goethals

Foreword — Animal experimentation is an emotional topic, which arouses passionate feelings both in animal protection groups and in the scientific community. For many years, antivivisectionists have fought for the abolition of all animal experimentation, whereas other groups campaign for suppression/reduction of the level of pain animals suffer because of experimentation. Despite all these efforts, the number of animals used in scientific research does not seem to have decreased significantly during the last few years. At best, this number remains constant or shows minor reductions in some countries, whereas in others it is still increasing. In addition to this situation, which certainly does not satisfy the antivivisectionists, the validity of the use of animal models in biomedical research is increasingly being questioned. On the other hand, a number of developments and projects exist which attest to the growing interest of scientists in in vitro models which use few, or even no, animals. Such a change in attitude is particularly evident in practice and research in toxicology, which uses a large number of animals. Taking into account the special status of toxicology among the biomedical sciences, since its practice is required and defined by laws and directives, a semantic problem exists over which adjective should be applied to describe such new methods. For some, it must be alternative — for consistancy to underline the possibility of replacing classical in vivo tests with new in vitro tests, the validity of which is demonstrated by reference to these in vivo tests. For others, it has to be complementary — to characterise the new protocols and the new experimental models which are of interest, because they contribute to the improvement of toxicology by strengthening its scientific nature. For a third group, it must be adjunct — to emphasise the relatively minor role of non-animal tests in relation to the conventional animal tests. It is the second concept that is favoured in this article. The experimental models to which it applies will, according to the Three Rs of Russell & Burch (1), lead either to the replacement of animal models, or to a reduction in the number of animals used or to refinement of test procedures in order to minimise the suffering and stress caused to animals.


2020 ◽  
Vol 88 (3) ◽  
pp. 32
Author(s):  
Eduardo Costa ◽  
Tânia Ferreira-Gonçalves ◽  
Gonçalo Chasqueira ◽  
António S. Cabrita ◽  
Isabel V. Figueiredo ◽  
...  

Breast cancer is one of the most common cancers worldwide, which makes it a very impactful malignancy in the society. Breast cancers can be classified through different systems based on the main tumor features and gene, protein, and cell receptors expression, which will determine the most advisable therapeutic course and expected outcomes. Multiple therapeutic options have already been proposed and implemented for breast cancer treatment. Nonetheless, their use and efficacy still greatly depend on the tumor classification, and treatments are commonly associated with invasiveness, pain, discomfort, severe side effects, and poor specificity. This has demanded an investment in the research of the mechanisms behind the disease progression, evolution, and associated risk factors, and on novel diagnostic and therapeutic techniques. However, advances in the understanding and assessment of breast cancer are dependent on the ability to mimic the properties and microenvironment of tumors in vivo, which can be achieved through experimentation on animal models. This review covers an overview of the main animal models used in breast cancer research, namely in vitro models, in vivo models, in silico models, and other models. For each model, the main characteristics, advantages, and challenges associated to their use are highlighted.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 975
Author(s):  
Somya Aggarwal ◽  
Ebrahim Hassan ◽  
Megan T. Baldridge

Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different in vitro and in vivo tools available to explore different pathophysiological attributes of human enteric RNA viruses, highlighting their advantages and limitations depending upon the question being explored. In addition, we discuss key areas and opportunities that would benefit from further methodological progress.


2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Abudujilili Abuduaini ◽  
Xueying Lu ◽  
Deng Zang ◽  
Tao Wu ◽  
Haji Akbar Aisa

Background. Kursi Karwiya or caraway tablet (CWT), a traditional medicine formula, is widely used in Xinjiang, China, for treating vitiligo, a common autoimmune disease for which there is currently no satisfactory cure. Clinical interventions include pharmacological treatment with psoralens, often in conjunction with UVA radiation, but toxic side effects limit this application. Studies on the activities and mechanisms of CWT are scarce. Objective. To investigate the in vitro and in vivo effects of CWT in B16 cell line and in animal models of vitiligo, further exploring its mechanisms of regulating melanogenesis. Methods. Effects of CWT on melanin synthesis in B16 cells and mushroom tyrosinase activity were investigated in vitro. The signaling pathway of melanogenesis in murine B16 melanoma cells was examined by Western blotting. Two different animal models were used, vitiligo induced by hydroquinone in the mouse model and by hydrogen peroxide in the guinea pig model. Relevant biochemical parameters in blood and skin tissue were measured, and visual inspection, histopathology, and immunohistochemical analysis of treated areas were carried out. Results. CWT produced changes in biochemical parameters including TYR, MDA, MAO, AChE, IL-6, INF-α, β-EP, and cAMP in blood and/or skin tissue and in regulating melanogenesis. After treatment with CTW, skin color, melanin containing hair follicles, and expression of TYR, TRP-1, and TRP-2 in the skin of animals were significantly affected. Conclusions. CWT alleviated many of detrimental effects in both models of vitiligo. Tyrosinase activity and melanin content in B16 cells were increased, at least in part, via activation of the PKA p38 MAPK signaling pathways. Our results show that CWT produces beneficial effects on parameters of vitiligo and is worthy of further investigation for use in this distressing autoimmune disorder which currently has no effective cure.


2020 ◽  
Author(s):  
Shahan Mamoor

COVID19 is caused by infection with the seventh virus of the coronavirus family capable of infecting humans, now known as Severe Acute Respiratory Syndrome 2, or SARS-CoV-2 (1-3). We mined published and public microarray data from coronavirus infection models to identify genes whose expression changed most significantly following infection with coronaviruses (4-9). In two in vivo mouse models of SARS coronavirus infection, the deubiquitinase USP18 was among the genes whose expression changed most significantly in the lungs of mice infected with SARS-CoV. In the blood of ferrets after intranasal infection with SARS-CoV-1, and in human cells in vitro after infection with the Middle Eastern Respiratory Syndrome (MERS) Usp18 was also found to be differentially expressed when compared to mock-infected tissues or uninfected cells. Differential expression of Usp18 following infection with coronaviruses can be observed in experimental models in vivo and in vitro, and across species.


1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.


2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.


2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.


2019 ◽  
Vol 14 (6) ◽  
pp. 504-518 ◽  
Author(s):  
Dilcele Silva Moreira Dziedzic ◽  
Bassam Felipe Mogharbel ◽  
Priscila Elias Ferreira ◽  
Ana Carolina Irioda ◽  
Katherine Athayde Teixeira de Carvalho

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords “ADIPOSE”, “CELLS”, and “PERIODONTAL”, with the Boolean operator “AND”. A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs.


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