scholarly journals Non-Human Primate Models of Enteric Viral Infections

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 544 ◽  
Author(s):  
Karol Sestak
Keyword(s):  
Gastrointestinal Tract ◽  
Biomedical Research ◽  
Human Disease ◽  
Viral Infections ◽  
Homo Sapiens ◽  
Model Studies ◽  
Research Outcomes ◽  
Clinical Systems ◽  
Human Primate ◽  
Made In

There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections including its applicability to human disease.

scholarly journals Non-Human Primate Models of Enteric Viral Infections

2018 ◽  
Author(s):  
Karol Sestak
Keyword(s):  
Gastrointestinal Tract ◽  
Biomedical Research ◽  
Human Disease ◽  
Viral Infections ◽  
Homo Sapiens ◽  
Model Studies ◽  
Research Outcomes ◽  
Clinical Systems ◽  
Human Primate ◽  
Made In

There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections and its applicability to human disease.

scholarly journals Human metapneumovirus - what we know now

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 135 ◽  
Author(s):  
Nazly Shafagati ◽  
John Williams
Keyword(s):  
Viral Infections ◽  
Clinical Manifestations ◽  
Adult Life ◽  
Small Animal ◽  
The Elderly ◽  
Human Metapneumovirus ◽  
Subtype C ◽  
Polymerase Chain ◽  
Human Primate ◽  
Made In

Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.

scholarly journals Combination therapy protects macaques against advanced Marburg virus disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Robert W. Cross ◽  
Zachary A. Bornholdt ◽  
Abhishek N. Prasad ◽  
Viktoriya Borisevich ◽  
Krystle N. Agans ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Rhesus Monkeys ◽  
Viral Infections ◽  
Virus Disease ◽  
Marburg Virus ◽  
Therapeutic Window ◽  
Post Inoculation ◽  
Primate Model ◽  
Lethal Infection ◽  
Human Primate

AbstractMonoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

scholarly journals Diagnosis and Therapeutic Management of Liver Fibrosis by microRNA

2021 ◽  
Vol 22 (15) ◽  
pp. 8139
Author(s):  
Tomoko Tadokoro ◽  
Asahiro Morishita ◽  
Tsutomu Masaki
Keyword(s):  
Liver Fibrosis ◽  
Viral Infections ◽  
Primary Biliary Cholangitis ◽  
Medical Need ◽  
Key Factor ◽  
Complications Of Cirrhosis ◽  
And Control ◽  
Functional Rnas ◽  
Remarkable Progress ◽  
Made In

Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called “exosomes” have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.

scholarly journals Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

2021 ◽  
Vol 22 (11) ◽  
pp. 6047
Author(s):  
Mattias F. Lindberg ◽  
Laurent Meijer
Keyword(s):  
Tyrosine Phosphorylation ◽  
Human Disease ◽  
Intracellular Signaling ◽  
Neuronal Development ◽  
Viral Infections ◽  
Current Knowledge ◽  
Lymphoblastic Leukemia ◽  
Cell Cycle Control ◽  
Megakaryoblastic Leukemia ◽  
Dual Specificity

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.

Plasmodium knowlesi: a relevant, versatile experimental malaria model

Parasitology ◽  
2016 ◽  
Vol 145 (1) ◽  
pp. 56-70 ◽  
Author(s):  
ERICA M. PASINI ◽  
ANNE-MARIE ZEEMAN ◽  
ANNEMARIE VOORBERG-VAN DER WEL ◽  
CLEMENS H. M. KOCKEN
Keyword(s):  
Parasite Species ◽  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Host Interactions ◽  
Model Studies ◽  
Human Red Blood Cells ◽  
Malaria Model ◽  
Human Primate

SUMMARYThe primate malariaPlasmodium knowlesihas a long-standing history as an experimental malaria model. Studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite–host interactions. The adaptation to long-termin vitrocontinuous blood stage culture in rhesus monkey,Macaca fascicularisand human red blood cells, as well as the development of various transfection methodologies has resulted in a highly versatile experimental malaria model, further increasing the potential of what was already a very powerful model. The growing evidence thatP. knowlesiis an important human zoonosis in South-East Asia has added relevance to former and future studies of this parasite species.

scholarly journals Coronavirus infection and gut microbiota

2021 ◽  
Vol 102 (4) ◽  
pp. 518-527
Author(s):  
D D Safina ◽  
S R Abdulkhakov
Keyword(s):  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Viral Infections ◽  
Subsequent Development ◽  
Upper Respiratory Tract ◽  
Therapeutic Approaches ◽  
Coronavirus Infection ◽  
Upper Respiratory ◽  
Treatment Of Infection ◽  
Tract Disorder

At present time, a number of questions regarding the pathophysiological characteristics and therapeutic approaches to the treatment of the new coronavirus infection COVID-19 remain unresolved. In some cases, patients with COVID-19 may experience symptoms of gastrointestinal tract disorder. According to the literature, the new SARS-CoV-2 coronavirus can replicate in the gastrointestinal tract and may affect the gut microbiota. The article aims to review studies about the possible relationship between the gut microbiota condition and the course of COVID-19 infection, as well as to consider the gut microbiota as a potential therapeutic target and probiotic drugs as possible therapeutic agents in the treatment of viral infections, including COVID-19 infection. It is known that gut microbiota condition is one of the factors determining the susceptibility and features of the bodys response to various infectious agents, possibly including the COVID-19 infection. Currently published studies demonstrate a possible relationship between the gut microbiota condition and the course of COVID-19 infection, however, to confirm this hypothesis, additional studies are required, which will allow to make more unambiguous conclusions with subsequent development of new approaches to the prevention and treatment of infection. Potentially a lot of hope in this direction is inspired by the results of probiotics studies, which showed that their use may reduce the frequency and severity of viral infections of the upper respiratory tract. However, currently, there is insufficient data to extrapolate the results of these studies to COVID-19 patients.

scholarly journals Conserved induction of distinct antiviral signalling kinetics by primate interferon lambda 4 proteins

2021 ◽  
Author(s):  
Cuncai Guo ◽  
Dorothee Reuss ◽  
Jonathon Dean Coey ◽  
Swathi Sukumar ◽  
Benjamin Lang ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Gastrointestinal Tract ◽  
Cell Types ◽  
Intestinal Cells ◽  
Wild Type ◽  
Sequence Identity ◽  
Functional Differences ◽  
Naturally Occurring ◽  
Barrier Tissues ◽  
Human Primate

Interferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver and gastrointestinal tract. Humans have four IFNλs (1-4) where IFNλ1-3 show ~80-95% homology and IFNλ4 is the most divergent displaying only ~30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFNλ4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study we address whether differences in antiviral signalling exist between IFNλ4 variants in human hepatocyte and intestinal cells, comparing them to IFNλ3. We demonstrate that compared to IFNλ3, wild-type human IFNλ4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally-occurring variants P70S and K154E in both cell types. IFNλ4s distinct antiviral response was more rapid yet transient compared to IFNλ1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFNλs and cell lines. Furthermore, an IFNλ4-like receptor-interacting interface failed to alter IFNλ1s kinetics. Together our data provide further evidence that major functional differences exist within the IFNλ gene family. These results highlight the possible tissue specialisation of IFNλs and encourage further investigation of the divergent, non-redundant activities of IFNλ4 and other IFNλs.

scholarly journals Original SARS-CoV-2 vaccine model

2020 ◽  
pp. 128-132
Author(s):  
I. E. Khoroshilov
Keyword(s):  
Immune System ◽  
Gastrointestinal Tract ◽  
Respiratory System ◽  
Clinical Picture ◽  
Viral Infections ◽  
Single Case ◽  
Viral Rna ◽  
Human Gastrointestinal Tract ◽  
Oral Transmission ◽  
Coronavirus Infection

The new coronavirus infection COVID-19 that appeared at the end of 2019 is signifi cantly different from the viral infections that existed previously. The new SARS-CoV-2 coronavirus combines two transmission routes—aerosol and oral-intestinal. The targets for this virus are both cells of the respiratory system and the human gastrointestinal tract. Along with the classical form of this disease, the so-called “gastrointestinal” form is described, in which the clinical picture is dominated by signs of damage to the gastrointestinal tract (diarrhea, vomiting, anorexia). These symptoms are detected, in general, in 20% of patients with COVID-19. More than 80% of patients have mild forms, a third of these individuals had diarrhea. Although SARSCoV-2 viral RNA is detected in faeces samples of patients with COVID-19, it does not carry an infectious onset, and not a single case of fecal-oral transmission has been confi rmed. Since the intestines are the most powerful organ of our immune system, we can introduce SARS-CoV-2 viral RNA into the gastrointestinal tract to ensure the formation of immunity to this infection.

Epistemology and the Ethics of Animal Experimentation

2021 ◽  
pp. 67-96
Author(s):  
Mylan Engel Jr.
Keyword(s):  
Animal Models ◽  
Biomedical Research ◽  
Human Disease ◽  
Animal Experiments ◽  
Animal Experimentation ◽  
Proper Treatment ◽  
Continued Use

In this chapter, Mylan Engel Jr. argues that animal experimentation is neither epistemically nor morally justified and should be abolished. Engel argues that the only serious attempt at justifying animal experimentation is the benefits argument, according to which animal experiments are justified because the benefits that humans receive from the experiments outweigh the costs imposed on the animal subjects. According to Engel, the benefits we allegedly receive from animal-based biomedical research are primarily epistemic, in that experimenting on animal models is supposed to provide us with knowledge of the origin and proper treatment of human disease. However, Engel argues that animal models are extremely unreliable at predicting how drugs will behave in humans, whether candidate drugs will be safe in humans, and whether candidate drugs will be effective in humans. Engel concludes that animal-based research fails to provide the epistemic, and thereby moral, benefits needed to justify its continued use.

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