44,219 results match your criteria rhesus macaques

Resolution of hepatitis E virus infection in CD8+ T cell depleted rhesus macaques.

J Hepatol 2021 May 4. Epub 2021 May 4.

Center for Vaccines and Immunity, The Research Institute at Nationwide Children's, 700 Children's Drive, Columbus, OH, USA; Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, USA. Electronic address:

Background And Aim: HEV is a significant cause of acute hepatitis globally. Some genotypes establish persistent infection when immunity is impaired. Adaptive immune mechanisms that mediate resolution of infection have not been identified. Read More

View Article and Full-Text PDF

Conjugates of Human Serum Butyrylcholinesterase and Nerve Agents are Behaviorally Safe in Rhesus Macaques.

Chem Biol Interact 2021 May 4:109499. Epub 2021 May 4.

US Army War College, Carlisle, PA 17013, USA.

Exogenously administered human serum butyrylcholinesterase (Hu BChE) affords protection by binding to organophosphorus (OP) nerve agents and pesticides in circulation. The resulting Hu BChE-OP conjugate undergoes 'aging' and the conjugate circulates until cleared from the body. Thus, we evaluated the effects of Hu BChE-OP conjugates on the general health and operant behavior of macaques. Read More

View Article and Full-Text PDF

Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques.

PLoS Pathog 2021 May 7;17(5):e1009575. Epub 2021 May 7.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, United States of America.

HIV-infected infants are at an increased risk of progressing rapidly to AIDS in the first weeks of life. Here, we evaluated immunological and virological parameters in 25 SIV-infected infant rhesus macaques to understand the factors influencing a rapid disease outcome. Infant macaques were infected with SIVmac251 and monitored for 10 to 17 weeks post-infection. Read More

View Article and Full-Text PDF

Postpubertal Spermatogonial Stem Cell Transplantation Restores Functional Sperm Production in Rhesus Monkeys Irradiated Before and After Puberty.

Andrology 2021 May 6. Epub 2021 May 6.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030.

Background: Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario.

Objectives: To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period. Read More

View Article and Full-Text PDF

Lack of Specific Regulatory T-Cell Depletion and Cytoreduction Associated with Extensive Toxicity after Administration of Low and High Doses of Cyclophosphamide.

AIDS Res Hum Retroviruses 2021 May 6. Epub 2021 May 6.

University of Pittsburgh, Division of Infectious Diseases, Pittsburgh, Pennsylvania, United States;

Up-to 93% of the HIV latent reservoir is comprised of defective proviruses, suggesting that a functional cure is possible through the elimination of a small population of cells containing intact virus, instead of the entire reservoir. Cyclophosphamide (Cy) is an established chemotherapeutic agent for immune cell cancers. In high doses, Cy is a nonselective cytoreductor, used in allogeneic stem-cell transplantation, while in a low dose, metronomic schedule, Cy selectively depletes regulatory T cells (Tregs). Read More

View Article and Full-Text PDF

Ultrasensitive detection and quantification of viral nucleic acids with raindance droplet digital PCR (ddPCR).

Methods 2021 May 3. Epub 2021 May 3.

AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, United States.

Sensitive detection of viral nucleic acids is critically important for diagnosis and monitoring of the progression of infectious diseases such as those caused by SARS-CoV2, HIV-1, and other viruses. In HIV-1 infection cases, assessing the efficacy of treatment interventions that are superimposed on combination antiretroviral therapy (cART) has benefited tremendously from the development of sensitive HIV-1 DNA and RNA quantitation assays. Simian immunodeficiency virus (SIV) infection of Rhesus macaques is similar in many key aspects to human HIV-1 infection and consequently this non-human primate (NHP) model has and continues to prove instrumental in evaluating HIV prevention, treatment and eradication approaches. Read More

View Article and Full-Text PDF

Comparative analysis reveals distinctive epigenetic features of the human cerebellum.

PLoS Genet 2021 May 6;17(5):e1009506. Epub 2021 May 6.

Department of Anthropology and Center for the Advanced Study of Human Paleobiology, The George Washington University, Washington, District of Columbia, United States of America.

Identifying the molecular underpinnings of the neural specializations that underlie human cognitive and behavioral traits has long been of considerable interest. Much research on human-specific changes in gene expression and epigenetic marks has focused on the prefrontal cortex, a brain structure distinguished by its role in executive functions. The cerebellum shows expansion in great apes and is gaining increasing attention for its role in motor skills and cognitive processing, including language. Read More

View Article and Full-Text PDF

The germline mutational process in rhesus macaque and its implications for phylogenetic dating.

Gigascience 2021 May;10(5)

Section for Ecology and Evolution, Department of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen Ø, Denmark.

Background: Understanding the rate and pattern of germline mutations is of fundamental importance for understanding evolutionary processes.

Results: Here we analyzed 19 parent-offspring trios of rhesus macaques (Macaca mulatta) at high sequencing coverage of ∼76× per individual and estimated a mean rate of 0.77 × 10-8de novo mutations per site per generation (95% CI: 0. Read More

View Article and Full-Text PDF

Preclinical evaluation for engraftment of CD34 cells gene-edited at the sickle cell disease locus in xenograft mouse and non-human primate models.

Cell Rep Med 2021 Apr 20;2(4):100247. Epub 2021 Apr 20.

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, USA.

Sickle cell disease (SCD) is caused by a 20A > T mutation in the β-globin gene. Genome-editing technologies have the potential to correct the SCD mutation in hematopoietic stem cells (HSCs), producing adult hemoglobin while simultaneously eliminating sickle hemoglobin. Here, we developed high-efficiency viral vector-free non-footprint gene correction in SCD CD34 cells with electroporation to deliver SCD mutation-targeting guide RNA, Cas9 endonuclease, and 100-mer single-strand donor DNA encoding intact β-globin sequence, achieving therapeutic-level gene correction at DNA (∼30%) and protein (∼80%) levels. Read More

View Article and Full-Text PDF

Effect of chronic ethanol consumption in rhesus macaques on the nucleus accumbens core transcriptome.

Addict Biol 2021 May 4:e13021. Epub 2021 May 4.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.

The nucleus accumbens core (NAcc) has been repeatedly demonstrated to be a key component of the circuitry associated with excessive ethanol consumption. Previous studies have illustrated that in a nonhuman primate (NHP) model of chronic ethanol consumption, there is significant epigenetic remodeling of the NAcc. In the current study, RNA-Seq was used to examine genome-wide gene expression in eight each of control, low/binge (LD*), and high/very high (HD*) rhesus macaque drinkers. Read More

View Article and Full-Text PDF

Infant rhesus macaques as a non-human primate model of Bordetella pertussis infection.

BMC Infect Dis 2021 May 3;21(1):407. Epub 2021 May 3.

Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, 650118, Yunnan, China.

Background: The prevalent resurgence of pertussis has recently become a critical public health problem worldwide. To understand pertussis pathogenesis and the host response to both the pathogen and vaccines, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a non-human primate pertussis model was successfully established with baboons. Read More

View Article and Full-Text PDF

Treatment of Limb Ischemia with Conducted Effects of Catheter-Based Endovascular Ultrasound.

Ultrasound Med Biol 2021 Apr 29. Epub 2021 Apr 29.

Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA; Oregon National Primate Research Center, Oregon Health & Science University, Portland, Oregon. Electronic address:

Ultrasound (US) is known to stimulate endogenous shear-dependent pathways, and can lower microvascular resistance through mediators that are conducted downstream from US exposure. We hypothesized that endovascular US, already in use for thrombolysis in humans, can improve tissue perfusion in the setting of acute limb ischemia through downstream-conducted effects. Models of severe peripheral arterial disease were developed in mice and in rhesus macaques. Read More

View Article and Full-Text PDF

Attention reduces the burstiness of V1 neurons involved in attended target enhancement.

Eur J Neurosci 2021 May 1. Epub 2021 May 1.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Attention-dependent reduction in the tendency for neurons to fire bursts (burstiness) is widely observed in the visual cortex. However, the underlying mechanism and the functional role of this phenomenon remain unclear. We recorded well-isolated single-unit activities in primary visual cortex (V1) from two primates (Macaca mulatta) while they performed a detection task engaging spatial attention with two levels of difficulty (hard/easy). Read More

View Article and Full-Text PDF

Transcriptomic phases of periodontitis lesions using the nonhuman primate model.

Sci Rep 2021 Apr 29;11(1):9282. Epub 2021 Apr 29.

Center for Oral Health Research College of Dentistry, University of Kentucky, Lexington, KY, USA.

We used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12-22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Read More

View Article and Full-Text PDF

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques.

Cells 2021 Apr 4;10(4). Epub 2021 Apr 4.

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA.

Transforming growth factor-β signaling (TGF-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-β promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-β production that attributes to its pathological manifestations remain unknown. Read More

View Article and Full-Text PDF

Comparison of three non-human primate aerosol models for glanders, caused by Burkholderia mallei.

Microb Pathog 2021 Apr 27;155:104919. Epub 2021 Apr 27.

Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA. Electronic address:

Burkholderia mallei is a gram-negative obligate animal pathogen that causes glanders, a highly contagious and potentially fatal disease of solipeds including horses, mules, and donkeys. Humans are also susceptible, and exposure can result in a wide range of clinical forms, i.e. Read More

View Article and Full-Text PDF

Animal Models of COVID-19 II. Comparative Immunology.

ILAR J 2021 Apr 29. Epub 2021 Apr 29.

Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.

Developing strong animal models is essential for furthering our understanding of how the immune system functions in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The alarming speed at which SARS-CoV-2 has spread, and the high mortality rate of severe Coronavirus Disease 2019 (COVID-19), has required both basic science and clinical research to move at an unprecedented pace. Models previously developed to study the immune response against SARS-CoV have been rapidly deployed to now study SARS-CoV-2. Read More

View Article and Full-Text PDF

Sustained fetal hemoglobin induction in vivo is achieved by interference and coexpressed truncated erythropoietin receptor.

Sci Transl Med 2021 Apr;13(591)

Cellular and Molecular Therapeutics Branch, National Heart Lung and Blood Institutes (NHLBI)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Hematopoietic stem cell gene therapy for hemoglobin disorders, including sickle cell disease, requires high-efficiency lentiviral gene transfer and robust therapeutic globin expression in erythroid cells. Erythropoietin is a key cytokine for erythroid proliferation and differentiation (erythropoiesis), and truncated human erythropoietin receptors (thEpoR) have been reported in familial polycythemia. We reasoned that coexpression of thEpoR could enhance the phenotypic effect of a therapeutic vector in erythroid cells in xenograft mouse and autologous nonhuman primate transplantation models. Read More

View Article and Full-Text PDF

Recombinant Herpesvirus Vectors: Durable Immune Responses and Durable Protection Against SIVmac239 Acquisition.

J Virol 2021 Apr 28. Epub 2021 Apr 28.

Department of Immunology and Microbiology, Scripps Research, Jupiter, Florida, USA.

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. Read More

View Article and Full-Text PDF

Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP.

J Exp Med 2021 07;218(7)

Biomedical Primate Research Centre, Rijswijk, Netherlands.

Safe and effective coronavirus disease-19 (COVID-19) vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26. Read More

View Article and Full-Text PDF

Protection against SARS-CoV-2 infection by a mucosal vaccine in rhesus macaques.

JCI Insight 2021 Apr 28. Epub 2021 Apr 28.

Vaccine Branch, Center for Cancer Research, NCI, NIH, Bethesda, United States of America.

Effective SARS-CoV-2 vaccines are urgently needed. While most vaccine strategies have focused on systemic immunization, here we compared the protective efficacy of two adjuvanted subunit vaccines with spike protein S1: an intramuscular (IM)- primed /boosted vaccine and an IM-primed/intranasal (IN)-boosted mucosal vaccine, in rhesus macaques. The IM-alum-only vaccine induced robust binding and neutralizing antibody and persistent cellular immunity systemically and mucosally, while IN boosting with nanoparticles including IL-15 and TLR agonists elicited weaker T-cell and antibody responses, but higher dimeric IgA and IFNa. Read More

View Article and Full-Text PDF

Longitudinal Profiling of the Macaque Vaginal Microbiome Reveals Similarities to Diverse Human Vaginal Communities.

mSystems 2021 Apr 27;6(2). Epub 2021 Apr 27.

Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, California, USA

The vaginal microbiota plays an important role in women's reproductive and urogenital health. It is now well accepted that a "healthy" vaginal microbiome is dominated by species. Disturbances in this microbial community can lead to several adverse outcomes, including pelvic inflammatory disease and bacterial vaginosis (BV), as well as increased susceptibility to sexually transmitted infections, miscarriage, and preterm births. Read More

View Article and Full-Text PDF

Predictors of Subcutaneous Injection Site Reactions to Sustained-Release Buprenorphine in Rhesus Macaques (Macaca mulatta).

J Am Assoc Lab Anim Sci 2021 Apr 27. Epub 2021 Apr 27.

Subcutaneous injection site reactions to sustained-release buprenorphine hydrochloride (Buprenorphine SR) in macaqueshave been reported in only a single case report. In the current study, we evaluated the incidence rate and predictors ofbuprenorphine SR reactions in the subcutaneous tissue of rhesus macaques (Macaca mulatta) based on retrospective reviewof macaque buprenorphine SR injection records. Potentially predictive variables were identified with logistic regressionmodeling and were evaluated using model selection based on Akaike information criterion. Read More

View Article and Full-Text PDF

HIV/SIV-infection induces opening of Pannexin-1 channels resulting in neuronal synaptic compromise: a novel therapeutic opportunity to prevent NeuroHIV.

J Neurochem 2021 Apr 26. Epub 2021 Apr 26.

Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.

In healthy conditions, pannexin-1 (Panx-1) channels are in a close state, but in several pathological conditions, including HIV and NeuroHIV, the channel becomes open. However, the mechanism or contribution of Panx-1 channels to the Human Immunodeficiency Virus-1 (HIV) pathogenesis and NeuroHIV are unknown. To determine the contribution of Panx-1 channels to the pathogenesis of NeuroHIV, we used a well-established model of Simian Immunodeficiency Virus (SIV) infection in macaques (Macaca mulatta) in the presence of and absence of a Panx-1 blocker to later examine the synaptic/axonal compromise induced for the virus. Read More

View Article and Full-Text PDF

Early Rearing Conditions Affect Monoamine Metabolite Levels During Baseline and Periods of Social Separation Stress: A Non-human Primate Model ().

Front Hum Neurosci 2021 9;15:624676. Epub 2021 Apr 9.

Department of Psychology, Brigham Young University, Provo, UT, United States.

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the "experience-expectant brain," with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. Read More

View Article and Full-Text PDF

The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys.

Signal Transduct Target Ther 2021 04 24;6(1):169. Epub 2021 Apr 24.

National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China.

Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. Read More

View Article and Full-Text PDF

Differences in host immune populations between rhesus macaques and cynomolgus macaque subspecies in relation to susceptibility to Mycobacterium tuberculosis infection.

Sci Rep 2021 Apr 23;11(1):8810. Epub 2021 Apr 23.

Public Health England - Porton, National Infections Service, Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Rhesus (Macaca mulatta) and cynomolgus (Macaca fasicularis) macaques of distinct genetic origin are understood to vary in susceptibility to Mycobacterium tuberculosis, and therefore differences in their immune systems may account for the differences in disease control. Monocyte:lymphocyte (M:L) ratio has been identified as a risk factor for M. tuberculosis infection and is known to vary between macaque species. Read More

View Article and Full-Text PDF

SARS-CoV-2 in animals: potential for unknown reservoir hosts and public health implications.

Vet Q 2021 Apr 23:1-31. Epub 2021 Apr 23.

Department of Agriculture, Faculty of Environmental Sciences, King Abdulaziz University, P.O. Box 80208, Jeddah 21589, Saudi Arabia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously 2019-nCoV) is suspected of having originated in 2019 in China from a coronavirus infected bat of the genus . Following the initial emergence, possibly facilitated by a mammalian bridge host, SARS-CoV-2 is currently transmitted across the globe via efficient human-to-human transmission. Results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters are susceptible to SARS-CoV-2 infection, and that cat-to-cat and ferret-to-ferret transmission can take place via contact and air. Read More

View Article and Full-Text PDF

A primary Chlamydia trachomatis genital infection of rhesus macaques identifies new immunodominant B-cell antigens.

PLoS One 2021 22;16(4):e0250317. Epub 2021 Apr 22.

Department of Pathology and Laboratory Medicine Medical Sciences I, University of California, Irvine, California, United States of America.

To identify immunodominant antigens that elicit a humoral immune response following a primary and a secondary genital infection, rhesus monkeys were inoculated cervically with Chlamydia trachomatis serovar D. Serum samples were collected and probed with a protein microarray expressing 864/894 (96.4%) of the open reading frames of the C. Read More

View Article and Full-Text PDF

Intradermal delivery of a synthetic DNA vaccine protects macaques from Middle East respiratory syndrome coronavirus.

JCI Insight 2021 Apr 22. Epub 2021 Apr 22.

Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, United States of America.

Emerging coronaviruses from zoonotic reservoirs including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been associated with human-to-human transmission and significant morbidity and mortality. Here we study both intradermal (ID) and intramuscular (IM) two-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV Spike (S) protein, which induced potent binding and neutralizing antibodies, as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared to controls. Read More

View Article and Full-Text PDF