145 results match your criteria tissues nhps

Identification and characterization of defective viral genomes in Ebola virus infected rhesus macaques.

J Virol 2021 Jun 23:JVI0071421. Epub 2021 Jun 23.

Boston University School of Medicine, Department of Microbiology, National Emerging Infectious Diseases Laboratory, 620 Albany St., Boston, MA 02118.

Ebola virus (EBOV), of the family is an RNA virus that can cause hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including  EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Read More

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Research Relevant Conditions and Pathology in Nonhuman Primates.

ILAR J 2021 Jun 15. Epub 2021 Jun 15.

Covance Preclinical Services GmbH, Münster 48163, Germany.

Biomedical research involving animal models continues to provide important insights into disease pathogenesis and treatment of diseases that impact human health. In particular, nonhuman primates (NHPs) have been used extensively in translational research due to their phylogenetic proximity to humans and similarities to disease pathogenesis and treatment responses as assessed in clinical trials. Microscopic changes in tissues remain a significant endpoint in studies involving these models. Read More

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Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers?

Front Pharmacol 2021 18;12:681477. Epub 2021 May 18.

School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.

Apigenin (4', 5, 7-trihydroxyflavone) is a plant flavone that has been found to have various actions against cancer cells. We evaluated available evidence to determine whether it is feasible for apigenin to have such effects in human patients. Apigenin taken orally is systemically absorbed and recirculated by enterohepatic and local intestinal pathways. Read More

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Monkeying around with MAIT Cells: Studying the Role of MAIT Cells in SIV and Mtb Co-Infection.

Viruses 2021 May 8;13(5). Epub 2021 May 8.

Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.

There were an estimated 10 million new cases of tuberculosis (TB) disease in 2019. While over 90% of individuals successfully control (Mtb) infection, which causes TB disease, HIV co-infection often leads to active TB disease. Despite the co-endemic nature of HIV and TB, knowledge of the immune mechanisms contributing to the loss of control of Mtb replication during HIV infection is lacking. Read More

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Para-chloro-2-[F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging.

Int J Med Sci 2021 21;18(10):2187-2196. Epub 2021 Mar 21.

Medicinal Chemistry and Uppsala University.

[C]Metomidate ([C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Read More

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Improved Detection of HIV Gag p24 Protein Using a Combined Immunoprecipitation and Digital ELISA Method.

Front Microbiol 2021 16;12:636703. Epub 2021 Mar 16.

Department of Infectious Disease and Vaccines, Merck & Co. Inc., Kenilworth, NJ, United States.

Greater than 90% of HIV-1 proviruses are thought to be defective and incapable of viral replication. While replication competent proviruses are of primary concern with respect to disease progression or transmission, studies have shown that even defective proviruses are not silent and can produce viral proteins, which may contribute to inflammation and immune responses. Viral protein expression also has implications for immune-based HIV-1 clearance strategies, which rely on antigen recognition. Read More

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Long-Term Safety Evaluation of Continuous Intraocular Delivery of Aflibercept by the Intravitreal Gene Therapy Candidate ADVM-022 in Nonhuman Primates.

Transl Vis Sci Technol 2021 Jan 29;10(1):34. Epub 2021 Jan 29.

Adverum Biotechnologies, Inc. Redwood City, CA USA.

Purpose: To evaluate the long-term safety of vascular endothelial growth factor (VEGF) suppression with sustained aflibercept expression after a single intravitreal injection (IVI) of ADVM-022, an anti-VEGF gene therapy, in non-human primates (NHPs).

Methods: Non-human primates received bilateral IVI of ADVM-022, a gene therapy vector encoding aflibercept, a standard of care for the treatment of VEGF-based retinal disease. Aflibercept levels from ocular fluids and tissues were measured. Read More

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January 2021

Transcriptional Analysis of Lymphoid Tissues from Infected Nonhuman Primates Reveals the Basis for Attenuation and Immunogenicity of an Ebola Virus Encoding a Mutant VP35 Protein.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Molecular Biology and Biochemistry, College of Biological Sciences, University of California, Irvine, Irvine, California, USA

Infection with (EBOV), a member of the family, causes a disease characterized by high levels of viremia, aberrant inflammation, coagulopathy, and lymphopenia. EBOV initially replicates in lymphoid tissues and disseminates via dendritic cells (DCs) and monocytes to liver, spleen, adrenal gland, and other secondary organs. EBOV protein VP35 is a critical immune evasion factor that inhibits type I interferon signaling and DC maturation. Read More

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February 2021

MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates.

Sci Transl Med 2020 11;12(569)

Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Delivering adeno-associated virus (AAV) vectors into the central nervous system of nonhuman primates (NHPs) via the blood or cerebral spinal fluid is associated with dorsal root ganglion (DRG) toxicity. Conventional immune-suppression regimens do not prevent this toxicity, possibly because it may be caused by high transduction rates, which can, in turn, cause cellular stress due to an overabundance of the transgene product in target cells. To test this hypothesis and develop an approach to eliminate DRG toxicity, we exploited endogenous expression of microRNA (miR) 183 complex, which is largely restricted to DRG neurons, to specifically down-regulate transgene expression in these cells. Read More

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November 2020

Growth hormone receptor knockout: Relevance to xenotransplantation.

Xenotransplantation 2021 Mar 14;28(2):e12652. Epub 2020 Oct 14.

Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.

Xenotransplantation research has made considerable progress in recent years, largely through the increasing availability of pigs with multiple genetic modifications, effective immunosuppressive therapy, and anti-inflammatory therapy to protect pig tissues from the primate immune and inflammatory responses and correct molecular incompatibilities. Further study is required regarding identification and investigation of physiological incompatibilities. Although the exact cause remains uncertain, we and others have observed relatively rapid growth of kidney xenografts after transplantation into nonhuman primates (NHPs). Read More

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Measles skin rash: Infection of lymphoid and myeloid cells in the dermis precedes viral dissemination to the epidermis.

PLoS Pathog 2020 10 8;16(10):e1008253. Epub 2020 Oct 8.

Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Measles is characterized by fever and a maculopapular skin rash, which is accompanied by immune clearance of measles virus (MV)-infected cells. Histopathological analyses of skin biopsies from humans and non-human primates (NHPs) with measles rash have identified MV-infected keratinocytes and mononuclear cells in the epidermis, around hair follicles and near sebaceous glands. Here, we address the pathogenesis of measles skin rash by combining data from experimentally infected NHPs, ex vivo infection of human skin sheets and in vitro infection of primary human keratinocytes. Read More

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October 2020

Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection.

Front Immunol 2020 18;11:2038. Epub 2020 Aug 18.

Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.

Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Read More

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Deep Learning for Automated Liver Segmentation to Aid in the Study of Infectious Diseases in Nonhuman Primates.

Acad Radiol 2020 Sep 14. Epub 2020 Sep 14.

Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases (NIAID), Frederick, MD, 21702, USA; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute (NCI), Frederick, MD, 21702, USA. Electronic address:

With the advent of deep learning, convolutional neural networks (CNNs) have evolved as an effective method for the automated segmentation of different tissues in medical image analysis. In certain infectious diseases, the liver is one of the more highly affected organs, where an accurate liver segmentation method may play a significant role to improve the diagnosis, quantification, and follow-up. Although several segmentation algorithms have been proposed for liver or liver-tumor segmentation in computed tomography (CT) of human subjects, none of them have been investigated for nonhuman primates (NHPs), where the livers have a wide range in size and morphology. Read More

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September 2020

Formation of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated by Expressed Determinants.

Front Immunol 2020 30;11:1325. Epub 2020 Jun 30.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States.

() is the causative agent of the infectious disease tuberculosis (TB), which is a leading cause of death worldwide. Approximately one fourth of the world's population is infected with . A major unresolved question is delineating the inducers of protective long-lasting immune response without inducing overt, lung inflammation. Read More

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Antiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and Humans.

Antimicrob Agents Chemother 2020 09 21;64(10). Epub 2020 Sep 21.

University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA

Adequate antiretroviral (ARV) concentrations in lymphoid tissues are critical for optimal antiretroviral therapy (ART). While the spleen contains 25% of the body's lymphocytes, there are minimal data on ARV penetration in this organ. This study quantified total and protein-unbound splenic ARV concentrations and determined whether drug transporters, sex, or infection status were modifiers of these concentrations in animal models and humans. Read More

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September 2020

Blood transcriptome analysis reveals gene expression features of breast-feeding rhesus macaque ( ) infants.

Zool Res 2020 Jul;41(4):431-436

Key Laboratory of Bioresources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, Sichuan 610065, China. E-mail:

During the breast-feeding period, infants undergo remarkable changes, including rapid physiological and developmental growth. However, little is known about gene expression features and sex-specific gene expression in breast-feeding infants. In this study, we sequenced 32 blood transcriptomes from 16 breast-feeding rhesus macaque ( ) infants and their lactating mothers. Read More

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Plasma and cerebrospinal fluid pharmacokinetics of the DNA methyltransferase inhibitor, 5-azacytidine, alone and with inulin, in nonhuman primate models.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa005. Epub 2020 Jan 1.

Pediatric Neuro-Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Background: Epigenetic modifiers are being investigated for a number of CNS malignancies as tumor-associated mutations such as isocitrate dehydrogenase mutations (IDH1/IDH2) and H3K27M mutations, which result in aberrant signaling, are identified. We evaluated the CNS exposure of the DNA methyltransferase inhibitor, 5-azacytidine (5-AZA), in preclinical nonhuman primate (NHP) models to inform its clinical development for CNS tumors.

Methods: 5-AZA and 5-AZA+Inulin pharmacokinetics (PK) were evaluated in NHPs ( = 10) following systemic (intravenous [IV]) and intrathecal (intraventricular [IT-V], intralumbar [IT-L], and cisternal [IT-C]) administration. Read More

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January 2020

Route of inoculation and mosquito vector exposure modulate dengue virus replication kinetics and immune responses in rhesus macaques.

PLoS Negl Trop Dis 2020 04 8;14(4):e0008191. Epub 2020 Apr 8.

GSK Vaccines, Rixensart, Belgium.

Dengue virus (DENV) is transmitted by infectious mosquitoes during blood-feeding via saliva containing biologically-active proteins. Here, we examined the effect of varying DENV infection modality in rhesus macaques in order to improve the DENV nonhuman primate (NHP) challenge model. NHPs were exposed to DENV-1 via subcutaneous or intradermal inoculation of virus only, intradermal inoculation of virus and salivary gland extract, or infectious mosquito feeding. Read More

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Resources for functional genomic studies of health and development in nonhuman primates.

Anna J Jasinska

Am J Phys Anthropol 2020 05 27;171 Suppl 70:174-194. Epub 2020 Mar 27.

Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Primates display a wide range of phenotypic variation underlaid by complex genetically regulated mechanisms. The links among DNA sequence, gene function, and phenotype have been of interest from an evolutionary perspective, to understand functional genome evolution and its phenotypic consequences, and from a biomedical perspective to understand the shared and human-specific roots of health and disease. Progress in methods for characterizing genetic, transcriptomic, and DNA methylation (DNAm) variation is driving the rapid development of extensive omics resources, which are now increasingly available from humans as well as a growing number of nonhuman primates (NHPs). Read More

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New Pathogenesis Mechanisms and Translational Leads Identified by Multidimensional Analysis of Necrotizing Myositis in Primates.

mBio 2020 02 18;11(1). Epub 2020 Feb 18.

Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, Texas, USA

A fundamental goal of contemporary biomedical research is to understand the molecular basis of disease pathogenesis and exploit this information to develop targeted and more-effective therapies. Necrotizing myositis caused by the bacterial pathogen is a devastating human infection with a high mortality rate and few successful therapeutic options. We used dual transcriptome sequencing (RNA-seq) to analyze the transcriptomes of and host skeletal muscle recovered contemporaneously from infected nonhuman primates. Read More

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February 2020

Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates.

Front Immunol 2019 23;10:3132. Epub 2020 Jan 23.

Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United States.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. Read More

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November 2020

Compromised steady-state germinal center activity with age in nonhuman primates.

Aging Cell 2020 02 15;19(2):e13087. Epub 2019 Dec 15.

Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.

Age-related reductions in vaccine-induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. Read More

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February 2020

Development of a nonhuman primate computational phantom for radiation dosimetry.

Med Phys 2020 Feb 29;47(2):736-744. Epub 2019 Dec 29.

Department of Medical Imaging and Information Sciences, Geneva University Hospital, Geneva, Switzerland.

Purpose: The nonhuman primate (NHP) is an important animal model for evaluating the response of the human body to radiation exposure owing to similarities between its organ structure, genome, life span, and metabolism. However, there is a lack of radiation dosimetry estimations for NHPs. The aim of this work is to construct a computational phantom of NHPs and estimate absorbed fractions and specific absorbed fractions for internal radiation dosimetry. Read More

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February 2020

Parsing the pluripotency continuum in humans and non-human primates for interspecies chimera generation.

Exp Cell Res 2020 02 26;387(1):111747. Epub 2019 Nov 26.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06511, USA. Electronic address:

Pluripotency refers to the potential of single cells to form all cells and tissues of an organism. The observation that pluripotent stem cells can chimerize the embryos of evolutionarily distant species, albeit at very low efficiencies, could with further modifications, facilitate the production of human-animal interspecies chimeras. The generation of human-animal interspecies chimeras, if achieved, will enable practitioners to recapitulate pathologic human tissue formation in vivo and produce patient-specific organs inside livestock species. Read More

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February 2020

Titin splicing regulates cardiotoxicity associated with calpain 3 gene therapy for limb-girdle muscular dystrophy type 2A.

Sci Transl Med 2019 11;11(520)

Généthon INSERM, U951, INTEGRARE Research Unit, Evry F-91002, France.

Limb-girdle muscular dystrophy type 2A (LGMD2A or LGMDR1) is a neuromuscular disorder caused by mutations in the calpain 3 gene (). Previous experiments using adeno-associated viral (AAV) vector-mediated calpain 3 gene transfer in mice indicated cardiac toxicity associated with the ectopic expression of the calpain 3 transgene. Here, we performed a preliminary dose study in a severe double-knockout mouse model deficient in calpain 3 and dysferlin. Read More

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November 2019

In-Vivo Gene Therapy with Foamy Virus Vectors.

Viruses 2019 11 23;11(12). Epub 2019 Nov 23.

Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e. Read More

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November 2019

Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates.

Sci Rep 2019 10 18;9(1):14960. Epub 2019 Oct 18.

Sanofi-Aventis, Frankfurt, Germany.

The glucagon receptor (GCGR) is an emerging target in anti-diabetic therapy. Reliable biomarkers for in vivo activity on the GCGR, in the setting of dual glucagon-like peptide 1/glucagon (GLP-1/GCG) receptor agonism, are currently unavailable. Here, we investigated [Ga]Ga-DO3A-S01-GCG as a biomarker for GCGR occupancy in liver, the tissue with highest GCGR expression, in non-human primates (NHP) by PET. Read More

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October 2019

Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice.

JCI Insight 2019 11 1;4(21). Epub 2019 Nov 1.

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.

Filoviruses of the genus Ebolavirus include 6 species with marked differences in their ability to cause disease in humans. From the highly virulent Ebola virus to the seemingly nonpathogenic Reston virus, case fatality rates can range between 0% and 90%. In order to understand the molecular basis of these differences, it is imperative to establish disease models that recapitulate human disease as faithfully as possible. Read More

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November 2019

Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model.

Reprod Biol Endocrinol 2019 Aug 24;17(1):70. Epub 2019 Aug 24.

Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, One Medical Center Blvd, Winston-Salem, NC, 27157, USA.

Background: Endometriosis is the growth of uterine lining (endometrium) outside of the uterus. In other chronic inflammatory diseases, mitochondrial dysfunction is suspected of playing a role in disease pathogenesis. However, little is known about endometriosis mitochondrial function or its effects on tissue metabolism. Read More

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Effect of dietary fat and sucrose consumption on cardiac fibrosis in mice and rhesus monkeys.

JCI Insight 2019 09 19;4(18). Epub 2019 Sep 19.

Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.

Calorie restriction (CR) improved health span in 2 longitudinal studies in nonhuman primates (NHPs), yet only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Here, analysis of left ventricle samples showed that CR did not reduce cardiac fibrosis relative to controls. However, there was a 5. Read More

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September 2019