alveolar macrophage dysfunction and increased pd-1 expression during chronic siv infection of rhesus macaques. | hiv infected individuals have been shown to be pre-disposed to pulmonary infections even while receiving anti-retroviral therapy. alveolar macrophages (ams) play a critical role in lung innate immunity, but contradictory results have been reported regarding their functionality following hiv infection. here, using the siv rhesus macaque model, we document the effect of siv infection on the phenotypic and functional properties of ams. following infection with sivmac251, ams in bronchoalveolar lava ... | 2019 | 31333668 |
macaques preferentially attend to visual patterns with higher fractal dimension contours. | animals' sensory systems evolved to efficiently process information from their environmental niches. niches often include irregular shapes and rough textures (e.g., jagged terrain, canopy outlines) that must be navigated to find food, escape predators, and master other fitness-related challenges. for most primates, vision is the dominant sensory modality and thus, primates have evolved systems for processing complicated visual stimuli. one way to quantify information present in visual stimuli in ... | 2019 | 31332197 |
preliminary assessment of the feasibility of autologous myeloid-derived suppressor cell infusion in non-human primate kidney transplantation. | myeloid-derived suppressor cells (mdsc) are a heterogenous population of immunosuppressive myeloid cells now considered important immune regulatory cells in diverse clinical conditions, including cancer, chronic inflammatory disorders and transplantation. in rodents, mdsc administration can inhibit graft-versus-host disease lethality and enhance organ or pancreatic islet allograft survival. there is also evidence, however, that under systemic inflammatory conditions, adoptively-transferred mdsc ... | 2019 | 31330261 |
behavioral changes and neuronal damage in rhesus monkeys after 10 weeks of ketamine administration involve prefrontal cortex dopamine d2 receptor and dopamine transporter. | the dopamine d2 receptor (drd2) and dopamine transporter (dat) play a regulatory role in dopaminergic neurotransmission and thus play an important role in drug addiction. the prefrontal cortex (pfc), a critical part of the mesencephalic dopaminergic system, is thought to be involved in the development and maintenance of drug addiction. the addiction to ketamine is thought to induce behavioral effects primarily through actions on the central nervous system. however, the neural mechanism underlyin ... | 2019 | 31330230 |
saccade variability in healthy subjects and cerebellar patients. | in a previous study we developed a model for the inter-trial variance of saccade trajectories in the rhesus macaque. the analysis of that model showed that signal-dependent noise results in different effector variabilities depending on whether the noise is propagated feedforward through the system (accumulating noise) or whether the noise originates from inside of a premotor feedback loop (feedback noise). this allowed the gain of the premotor feedback loop to be estimated directly from behavior ... | 2019 | 31325974 |
development of a gold nanoparticle-functionalized surface plasmon resonance assay for the sensitive detection of monoclonal antibodies and its application in pharmacokinetics. | as a prominent human therapeutic, therapeutic monoclonal antibodies (mabs) have attracted increasing attention in the past decade due to their high-targeting specificity, low toxicity, and prolonged efficacy. systematic pharmacokinetic analysis of mabs not only largely facilitates the understanding of their biologic functions but also promotes the development of therapeutic drug discovery, early clinical trial implementation, and therapeutic monitoring. however, the extremely complex nature of b ... | 2019 | 31324700 |
chronic binge alcohol-associated differential brain region modulation of growth factor signaling pathways and neuroinflammation in simian immunodeficiency virus-infected male macaques. | microarray analysis of hippocampal tissue from chronic binge alcohol (cba)-administered, simian immunodeficiency virus (siv)-infected male macaques identified altered immune response and neurogenesis as potential mechanisms underlying cognitive deficits in macaques. this study investigated the differential brain region associations between markers of neuroinflammation and growth factor signaling with microtubule-associated protein 2 (map2) expression. | 2019 | 31322648 |
mhc genotyping from rhesus macaque exome sequences. | indian rhesus macaque major histocompatibility complex (mhc) variation can influence the outcomes of transplantation and infectious disease studies. frequently, rhesus macaques are mhc genotyped to identify variants that could account for unexpected results. since the mhc is only one region in the genome where variation could impact experimental outcomes, strategies for simultaneously profiling variation in the macaque mhc and the remainder of the protein coding genome would be useful. here we d ... | 2019 | 31321455 |
an asymmetry of treatment between lotteries involving gains and losses in rhesus monkeys. | decision-making in humans is known to be subject to several biases. for instance, when facing bets, humans demonstrate some asymmetry concerning their preference for the riskiest option depending on whether stakes involve potential gains or potential losses. they are indeed risk-averse for bets involving gains but risk seeking for bets involving losses. they also exhibit a distorted perception of probabilities. it is not clear whether non-human primates exhibit the same biases. setting up a prot ... | 2019 | 31320725 |
social status and gene regulation: conservation and context dependence in primates. | current models suggest that low social status affects immune function by increasing inflammation and compromising antiviral defense. while this pattern appears to be somewhat conserved, recent studies argue that the gene regulatory signature of social status also depends on the local environment and the nature of social hierarchies. | 2019 | 31320266 |
a live-attenuated rhcmv/siv vaccine shows long-term efficacy against heterologous siv challenge. | previous studies have established that strain 68-1-derived rhesus cytomegalovirus (rhcmv) vectors expressing simian immunodeficiency virus (siv) proteins (rhcmv/siv) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic siv in rhesus monkeys (rms). however, these efficacious rhcmv/siv vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. to develop a ... | 2019 | 31316007 |
enhancing safety of cytomegalovirus-based vaccine vectors by engaging host intrinsic immunity. | rhesus cytomegalovirus (rhcmv)-based vaccines maintain effector memory t cell responses (tem) that protect ~50% of rhesus monkeys (rms) challenged with simian immunodeficiency virus (siv). because human cmv (hcmv) causes disease in immunodeficient subjects, clinical translation will depend upon attenuation strategies that reduce pathogenic potential without sacrificing cmv's unique immunological properties. we demonstrate that "intrinsic" immunity can be used to attenuate strain 68-1 rhcmv vecto ... | 2019 | 31316006 |
vaccine-mediated inhibition of the transporter associated with antigen processing is insufficient to induce major histocompatibility complex e-restricted cd8+ t cells in nonhuman primates. | major histocompatibility complex e (mhc-e) is a highly conserved nonclassical mhc-ib molecule that tightly binds peptides derived from leader sequences of classical mhc-ia molecules for presentation to natural killer cells. however, mhc-e also binds diverse foreign and neoplastic self-peptide antigens for presentation to cd8+ t cells. although the determinants of mhc-e-restricted t cell priming remain unknown, these cells are induced in humans infected with pathogens containing genes that inhibi ... | 2019 | 31315990 |
differential dynamics of regulatory t-cell and th17 cell balance in mesenteric lymph nodes and blood following early antiretroviral initiation during acute simian immunodeficiency virus infection. | increased frequencies of immunosuppressive regulatory t cells (tregs) are associated with gut lymphoid tissue fibrosis and dysfunction which, in turn, contribute to disease progression in chronic simian immunodeficiency virus/human immunodeficiency virus (siv/hiv) infection. mesenteric lymph nodes (mlns), which drain the large and small intestine, are critical sites for the induction and maintenance of gut mucosal immunity. however, the dynamics of tregs in mlns are not well understood due to th ... | 2019 | 31315987 |
factors determining male introduction success and long-term stability in captive rhesus macaques. | the entrance of new males into non-human primate groups bears high social risk, yet migration is necessary to prevent inbreeding. males are not always accepted in their new group. in the wild, males may increase the likelihood of successful group entry by choosing a new group based on their own and the group's characteristics. understanding whether these characteristics also determine a male's ability to enter captive groups is crucial to improve introduction management. this study aims to ident ... | 2019 | 31314795 |
hla class ii-restricted cd8+ t cells in hiv-1 virus controllers. | a paradigm shifting study demonstrated that induction of mhc class e and ii-restricted cd8+ t cells was associated with the clearance of siv infection in rhesus macaques. another recent study highlighted the presence of hiv-1-specific class ii-restricted cd8+ t cells in hiv-1 patients who naturally control infection (virus controllers; vcs). however, questions regarding class ii-restricted cd8+ t cells ontogeny, distribution across different hiv-1 disease states and their role in viral control r ... | 2019 | 31308388 |
revealing uninfected and infected target cell dynamics from peripheral blood data in highly and less pathogenic simian/human immunodeficiency virus infected rhesus macaque. | since chimeric simian and human immunodeficiency viruses (shivs) used here, that is, shiv-#64 and -ks661 utilize both ccr5 and cxcr4 chemokine receptors, they have broad target cell properties. a highly pathogenic shiv strain, shiv-ks661, causes an infection that systemically depletes the cd4+ t cells of rhesus macaques, while a less pathogenic strain, shiv-#64, does not cause severe symptoms in the macaques. in our previous studies, we established in vitro quantification system for virus infect ... | 2019 | 31299334 |
effects of the synthetic cannabinoid receptor agonist jwh-018 on abuse-related effects of opioids in rhesus monkeys. | opioid abuse remains a public health crisis despite a tremendous outpouring of resources to address the problem. one factor that might complicate this issue is polydrug abuse. while cannabis is increasingly available due to legalization by states, phytocannabinoids do not appear to alter the abuse-related effects of opioids. synthetic cannabinoids, which are not pharmacologically identical to phytocannabinoids, are also increasingly available, and differences among cannabinoids might affect thei ... | 2019 | 31295696 |
monkey eeg links neuronal color and motion information across species and scales. | it remains challenging to relate eeg and meg to underlying circuit processes and comparable experiments on both spatial scales are rare. to close this gap between invasive and non-invasive electrophysiology we developed and recorded human-comparable eeg in macaque monkeys during visual stimulation with colored dynamic random dot patterns. furthermore, we performed simultaneous microelectrode recordings from 6 areas of macaque cortex and human meg. motion direction and color information were acce ... | 2019 | 31287792 |
characterization of heart macrophages in rhesus macaques as a model to study cardiovascular disease in humans. | rhesus macaques are physiologically similar to humans and, thus, have served as useful animal models of human diseases including cardiovascular disease. the purpose of this study was to characterize the distribution, composition, and phenotype of macrophages in heart tissues of very young (fetus: 0.5 years, n = 6), young adult (2-12 years, n = 12), and older adult (13-24 years, n = 9) rhesus macaques using histopathology and immunofluorescence microscopy. results demonstrated that macrophages we ... | 2019 | 31287581 |
kynurenine 3-monooxygenase inhibition during acute simian immunodeficiency virus infection lowers pd-1 expression and improves post-combination antiretroviral therapy cd4+ t cell counts and body weight. | the kynurenine pathway (kp) is a key regulator of many important physiological processes and plays a harmful role in cancer, many neurologic conditions, and chronic viral infections. in hiv infection, kp activity is consistently associated with reduced cd4 t cell counts and elevated levels of t cell activation and viral load; it also independently predicts mortality and morbidity from non-aids events. kynurenine 3-monooxygenase (kmo) is a therapeutically important target in the kp. using the non ... | 2019 | 31285277 |
identifying micrornas and their editing sites in macaca mulatta. | micrornas (mirnas) are small non-coding rnas that are critical in post-transcriptional regulation. macaca mulatta is an important nonhuman primate that is often used in basic and translational researches. however, the annotation of mirnas in macaca mulatta is far from complete, and there are no reports of mirna editing events in macaca mulatta, although editing may affect the biogenesis or functions of the mirnas. to improve mirna annotation and to reveal editing events of mirnas in macaca mulat ... | 2019 | 31284505 |
mesenchymal derived exosomes enhance recovery of motor function in a monkey model of cortical injury. | exosomes from mesenchymal stromal cells (mscs) are endosome-derived vesicles that have been shown to enhance functional recovery in rodent models of stroke. | 2019 | 31282441 |
navigation strategy in macaque monkeys: an exploratory experiment in virtual reality. | spatial memory and navigation have been widely studied using animal models, most of them were performed with rodents and only few of them with non-human primates. also, most of these studies were achieved in simple and small-scale mazes. | 2019 | 31276693 |
evaluation of a motion-robust 2d chemical shift-encoded technique for r2* and field map quantification in ferumoxytol-enhanced mri of the placenta in pregnant rhesus macaques. | 3d chemical shift-encoded (cse)-mri techniques enable assessment of ferumoxytol concentration but are unreliable in the presence of motion. | 2020 | 31276263 |
antiretroviral therapy administration in healthy rhesus macaques is associated with transient shifts in intestinal bacterial diversity and modest immunological perturbations. | gastrointestinal (gi) immune system competency is dependent upon interactions with commensal microbiota, which can be influenced by wide-ranging pharmacologic interventions. in simian immunodeficiency virus (siv)-infected asian macaque models of human immunodeficiency virus (hiv) infection, we previously noted that initiation of antiretroviral therapy (art) is associated with a specific imbalance (dysbiosis) of the composition of the intestinal bacteriome. to determine if art itself might contri ... | 2019 | 31270225 |
siv-mediated synaptic dysfunction is associated with an increase in synapsin site 1 phosphorylation and impaired pp2a activity. | although the reduction of viral loads in people with hiv undergoing combination antiretroviral therapy has mitigated aids-related symptoms, the prevalence of neurological impairments has remained unchanged. hiv-associated cns dysfunction includes impairments in memory, attention, memory processing, and retrieval. here, we show a significant site-specific increase in the phosphorylation of syn i serine 9, site 1, in the frontal cortex lysates and synaptosome preparations of male rhesus macaques i ... | 2019 | 31270156 |
refinements of equipment and methodology to reduce risk during pole-guided chair transfer of nonhuman primates. | neurophysiologic studies of nhp commonly involve their transfer from a housing enclosure to a laboratory by using a mobile chair. this transfer should be performed in a manner that is safe and minimizes stress for both animal and handler. the risk of harm associated with attempting to transfer these animals is increased when they are mature and naïve. we have modified previous chair designs and transfer methodologies to reduce this risk by maintaining a constant barrier between nhp and handler w ... | 2019 | 31270007 |
pharmacological validation of a translational model of cocaine use disorder: effects of d-amphetamine maintenance on choice between intravenous cocaine and a nondrug alternative in humans and rhesus monkeys. | drug self-administration procedures are the gold standard for laboratory research to study mechanisms of drug use disorders and evaluate candidate medications. however, preclinical-to-clinical translation has been hampered by a lack of coordination. to address this limitation, we previously developed homologous intravenous (iv) cocaine choice self-administration procedures in rhesus monkeys and humans, and then demonstrated their functional equivalence. the present studies sought to determine th ... | 2020 | 31259593 |
[18f]gtp1 (genentech tau probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in alzheimer's disease. | neurofibrillary tangles (nfts), consisting of intracellular aggregates of the tau protein, are a pathological hallmark of alzheimer's disease (ad). here we report the identification and initial characterization of genentech tau probe 1 ([18f]gtp1), a small-molecule pet probe for imaging tau pathology in ad patients. | 2019 | 31254035 |
busulfan combined with immunosuppression allows efficient engraftment of gene-modified cells in a rhesus macaque model. | busulfan conditioning is utilized for hematopoietic stem cell (hsc) depletion in the context of hsc gene-therapy conditioning but may result in insufficient immunosuppression. in this study, we evaluated whether additional immunosuppression is required for efficient engraftment of gene-modified cells using a rhesus hsc lentiviral gene-therapy model. we transduced half of rhesus cd34+ cells with an enhanced green fluorescent protein (gfp)-encoding vector (immunogenic) and the other half with a γ- ... | 2019 | 31253582 |
acute suppression of insulin resistance-associated hepatic mir-29 in vivo improves glycemic control in adult mice. | micrornas (mirnas) are important posttranscriptional regulators of metabolism and energy homeostasis. dysregulation of certain mirnas in the liver has been shown to contribute to the pathogenesis of type 2 diabetes (t2d), in part by impairing hepatic insulin sensitivity. by small rna-sequencing analysis, we identified seven hepatic mirnas (including mir-29b) that are consistently aberrantly expressed across five different rodent models of metabolic dysfunction that share the feature of insulin r ... | 2019 | 31251698 |
development and validation of a primate model for liver fibrosis. | many liver diseases involve liver fibrosis. most preclinical studies of liver fibrosis are carried out in small animals such as rodents, and thus lack direct potential for extrapolation to human diseases. the aim of the current study was to develop a primate model for liver fibrosis with greater relevance to translational research. | 2020 | 31247307 |
vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of parkinson's disease. | ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-dopa) therapy has retained its role as the leading standard medication for patients with parkinson's disease. with time, however, the shortcomings of oral l-dopa treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. these side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-dopa ... | 2019 | 31243443 |
gene expression across mammalian organ development. | the evolution of gene expression in mammalian organ development remains largely uncharacterized. here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events ... | 2019 | 31243369 |
developmental dynamics of lncrnas across mammalian organs and species. | although many long noncoding rnas (lncrnas) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. in particular, the contribution of lncrnas to organ development remains largely unexplored. here we analyse the expression patterns of lncrnas across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chick ... | 2019 | 31243368 |
dominance rank predicts social network position across developmental stages in rhesus monkeys. | social network analysis is increasingly common in studying complex interactions among individuals. across a range of primates, high-ranking adults are generally more socially connected, which results in better fitness outcomes. however, it still remains unclear whether this relationship between social network position and dominance rank emerges in infancy and whether, in species with a social transmission of dominance rank, social network positions are driven by the presence of the mother. to fi ... | 2020 | 31240764 |
discriminative stimulus effects and metabolism of ethanol in rhesus monkeys. | animal models are an essential feature of drug and pharmacotherapy development for treating alcohol use disorders (auds). the rhesus macaque is a robust animal model for many aspects of auds particularly in exploiting individual differences in oral self-administration of ethanol (etoh), endocrine orchestration of stress response, and menstrual cycle characteristics. however, the clearance rates of etoh have not been reported in this species, and the gabaa and n-methyl-d-aspartate (nmda) receptor ... | 2019 | 31237691 |
chondroitinase improves anatomical and functional outcomes after primate spinal cord injury. | inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after cns injury. the enzyme chondroitinase (chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. we evaluated the effects of chase in rhesus monkeys that had undergone c7 spinal cord hemisection. four weeks after hemisection, we administered mul ... | 2019 | 31235933 |
bisphenol a-induced apoptosis, oxidative stress and dna damage in cultured rhesus monkey embryo renal epithelial marc-145 cells. | bisphenol a (bpa) is widely used in the production of epoxy resins and polycarbonate plastics. under harsh situations, these plastics likely desorb bpa, which then can seep into the environment. various concentrations of bpa have been detected in most biological fluid. however, there is paucity of information on the detrimental effects of bpa and its subsequent cellular events in chronic kidney disease (ckd). hence, in this in vitro study, we aimed to investigate the effects of bpa on renal epit ... | 2019 | 31234085 |
comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates. | humans carry a much larger percentage of body fat than other primates. despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. we examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using rhesus macaque as an outgroup. we f ... | 2019 | 31233101 |
what can we learn about human individual face recognition from experimental studies in monkeys? | typical human adults recognize numerous individuals from their faces accurately, rapidly and automatically, reaching a level of expertise at individual face recognition that is important for the quality of their social interactions. a non-human species of primates, the rhesus monkey, has been used for decades as a model of human face processing, in particular for understanding the neural basis of individual face recognition. however, despite responding specifically to faces behaviourally and neu ... | 2019 | 31230664 |
in vitro culture of rhesus macaque (macaca mulatta) embryos. | production of nonhuman primate (nhp) embryos in vitro begins with recovery of gametes. females undergo a controlled ovary stimulation to produce multiple preovulatory follicles from which oocytes may be recovered. mature ova are subjected to in vitro fertilization (ivf) and presumptive zygotes are cultured to the intended stage of development. essential to this practice is the culture medium unique to each step in the process. here we describe medium preparation, oocyte recovery, in vitro fertil ... | 2019 | 31230291 |
a parameterized digital 3d model of the rhesus macaque face for investigating the visual processing of social cues. | rhesus macaques are the most popular model species for studying the neural basis of visual face processing and social interaction using intracranial methods. however, the challenge of creating realistic, dynamic, and parametric macaque face stimuli has limited the experimental control and ethological validity of existing approaches. | 2019 | 31229584 |
dosing and formulation of antenatal corticosteroids for fetal lung maturation and gene expression in rhesus macaques. | antenatal corticosteroids (ans) are the major intervention to decrease respiratory distress syndrome and mortality from premature birth and are standard of care. the use of ans is expanding to include new indications and gestational ages, although the recommended dosing was never optimized. the most widely used treatment is two intramuscular doses of a 1:1 mixture of betamethasone-phosphate (beta-p) and betamethasone-acetate (beta-ac) - the clinical drug. we tested in a primate model the efficac ... | 2019 | 31227752 |
daratumumab in sensitized kidney transplantation: potentials and limitations of experimental and clinical use. | donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. therefore, reducing the risk of these antibodies remains a clinical need in transplantation. plasma cells are a logical target of therapy given their critical role in antibody production. | 2019 | 31227636 |
pharmacokinetics of a long-lasting, highly concentrated buprenorphine solution after subcutaneous administration in rhesus macaques (macaca mulatta). | opioids are essential for use in rhesus macaques (macaca mulatta) that require multimodal analgesia or those unable to receive nsaid as part of their pain management plan. the current opioid epidemic has universally limited the availability of these vital analgesics, compelling clinicians to investigate other options including novel opioid formulations. a commercially available injectable, long-lasting, highly concentrated buprenorphine solution (hcbs) provides therapeutic plasma concentrations ... | 2019 | 31227029 |
the levels of the nmda receptor co-agonist d-serine are reduced in the substantia nigra of mptp-lesioned macaques and in the cerebrospinal fluid of parkinson's disease patients. | dysfunction of nmda receptor (nmdar)-mediated transmission is supposed to contribute to the motor and non-motor symptoms of parkinson's disease (pd), and to l-dopa-induced dyskinesia. besides the main agonist l-glutamate, two other amino acids in the atypical d-configuration, d-serine and d-aspartate, activate nmdars. in the present work, we investigated the effect of dopamine depletion on d-amino acids metabolism in the brain of mptp-lesioned macaca mulatta, and in the serum and cerebrospinal f ... | 2019 | 31222058 |
the role of human cd46 in early xenoislet engraftment in a dual transplant model. | membrane cofactor protein cd46 attenuates the complement cascade by facilitating cleavage of c3b and c4b. in solid organ xenotransplantation, organs expressing cd46 have been shown to resist hyperacute rejection. however, the incremental value of human cd46 expression for islet xenotransplantation remains poorly defined. | 2019 | 31219218 |
individual neurons in the cingulate cortex encode action monitoring, not selection, during adaptive decision-making. | the cingulate cortex contributes to complex, adaptive behaviors, but the exact nature of its contributions remains unresolved. proposals from previous studies, including evaluating past actions or selecting future ones, have been difficult to distinguish in part because of an incomplete understanding of the task-relevant variables that are encoded by individual cingulate neurons. in this study, we recorded from individual neurons in parts of both the anterior cingulate cortex (acc) and posterior ... | 2019 | 31217329 |
simian-human immunodeficiency virus shiv.ch505 infection of rhesus macaques results in persistent viral replication and induces intestinal immunopathology. | simian-human immunodeficiency viruses (shivs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. however, the majority of shivs currently available have significant limitations in that they were developed using sequences from chronically hiv-infected individuals or uncommon hiv subtypes or were optimized for the macaque model by serially passaging the engineered virus in vitro or in vivo recently, a newly developed shiv, shiv.c.ch505.3 ... | 2019 | 31217249 |
pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. | purpose: evaluation of the pharmacodynamics (pd) and pharmacokinetics (pk) of romiplostim alone and in combination with pegfilgrastim in a non-human primate (nhp) model of acute radiation syndrome (ars).materials and methods: male and female rhesus macaques were subjected to cobalt-60 γ irradiation, at a dose of 550 cgy 24 h prior to subcutaneous administration of either romiplostim alone as a single (2.5 or 5.0 mg/kg on day 1) or repeat dose (5.0 mg/kg on days 1 and 8), pegfilgrastim alone as a ... | 2020 | 31216213 |
a connectional hub in the rostral anterior cingulate cortex links areas of emotion and cognitive control. | we investigated afferent inputs from all areas in the frontal cortex (fc) to different subregions in the rostral anterior cingulate cortex (racc). using retrograde tracing in macaque monkeys, we quantified projection strength by counting retrogradely labeled cells in each fc area. the projection from different fc regions varied across injection sites in strength, following different spatial patterns. importantly, a site at the rostral end of the cingulate sulcus stood out as having strong inputs ... | 2019 | 31215864 |
bioreducible poly(urethane amine)s for robust nucleic acid transfection in stem cells. | the search for cationic polymeric carriers enabling robust gene transfection against stem cells remains a challenge. herein, linear bioreducible poly(urethane amine)s (denoted as sspuas) with repeated disulfide and protonable amino groups were prepared and used as non-viral vectors for in vitro gene transfection of different stem cells. the polyurethane copolymers (denoted as ssbt) with varied molar ratios of 1,4-bis(3-aminopropyl)piperazine (bap) and tris(2-aminoethyl) amine (taa) moieties coul ... | 2019 | 31215549 |
a meningococcal outer membrane vesicle vaccine with overexpressed mutant fhbp elicits higher protective antibody responses in infant rhesus macaques than a licensed serogroup b vaccine. | menb-4c (bexsero; glaxosmithkline biologicals) is a licensed meningococcal vaccine for capsular b strains. the vaccine contains detergent-extracted outer membrane vesicles (domv) and three recombinant proteins, of which one is factor h binding protein (fhbp). in previous studies, overexpression of fhbp in native omv (nomv) with genetically attenuated endotoxin (lpxl1) and/or by the use of mutant fhbp antigens with low factor h (fh) binding increased serum bactericidal antibody (sba) responses. i ... | 2019 | 31213564 |
modelling disease risk for amyloid a (aa) amyloidosis in non-human primates using machine learning. | objective: amyloid a (aa) amyloidosis is found in humans and non-human primates, but quantifying disease risk prior to clinical symptoms is challenging. we applied machine learning to identify the best predictors of amyloidosis in rhesus macaques from available clinical and pathology records. to explore potential biomarkers, we also assessed whether changes in circulating serum amyloid a (saa) or lipoprotein profiles accompany the disease. methods: we conducted a retrospective study using 86 cas ... | 2019 | 31210531 |
a novel astrovirus identified in wild rhesus monkey feces in china. | the discovery and analysis of pathogens carried by non-human primates are important for understanding zoonotic infections in humans. we identified a highly divergent astrovirus (astv) from fecal matter from a rhesus monkey in china, which has been tentatively named "monkey-feces-associated astv" (mkastv). the full-length genome of mkastv was determined to be 7377 nt in length. it exhibits the standard genomic astv organization of three open reading frames (orfs) and is most closely related to du ... | 2019 | 31209596 |
occurrence of selected zoonotic fecal pathogens and first molecular identification of hafnia paralvei in wild taihangshan macaques (macaca mulatta tcheliensis) in china. | rhesus macaques (macaca mulatta) are hosts to a range of zoonotic and potentially zoonotic pathogens. the present study firstly provides a broader investigation of the presence and prevalence of zoonotic fecal pathogens in wild taihangshan macaques, a subspecies of rhesus macaque in china. a total of 458 fecal samples were collected between september 2015 and november 2016. fourteen genera of intestinal parasites (four genera of protozoans and ten genera of helminths) and twelve genera of bacter ... | 2019 | 31205937 |
coding strategies in the otolith system differ for translational head motion vs. static orientation relative to gravity. | the detection of gravito-inertial forces by the otolith system is essential for our sense of balance and accurate perception. to date, however, how this system encodes the self-motion stimuli that are experienced during everyday activities remains unknown. here, we addressed this fundamental question directly by recording from single otolith afferents in monkeys during naturalistic translational self-motion and changes in static head orientation. otolith afferents with higher intrinsic variabili ... | 2019 | 31199243 |
subcortical substrates of explore-exploit decisions in primates. | the explore-exploit dilemma refers to the challenge of deciding when to forego immediate rewards and explore new opportunities that could lead to greater rewards in the future. while motivational neural circuits facilitate learning based on past choices and outcomes, it is unclear whether they also support computations relevant for deciding when to explore. we recorded neural activity in the amygdala and ventral striatum of rhesus macaques as they solved a task that required them to balance nove ... | 2019 | 31196672 |
comparative analysis of the germinal center response by flow cytometry and immunohistology. | germinal centers (gcs) are structures formed within b cell follicles critical for the generation of high affinity antibodies. the evaluation of gcs in secondary lymphoid tissues has emerged as a valuable means for understanding the immunological activity in vaccine responses, autoimmunity and cancer. the analysis has been facilitated by advances in sampling techniques, including non-invasive lymph node collection and fine needle aspiration. in this study, we performed a systematic comparison bet ... | 2019 | 31194971 |
gut microbiome alterations during hiv/siv infection: implications for hiv cure. | gut mucosal damage, associated with human immunodeficiency virus-1 (hiv) infection, is characterized by depletion in cd4+ t cells and persistent immune activation as a result of early epithelial barrier disruption and systemic translocation of microbial products. unique approaches in studying both hiv infection in human patients and simian immunodeficiency virus (siv) infection in rhesus macaques have provided critical evidence for the pathogenesis and treatment of hiv/aids. while there is vast ... | 2019 | 31191468 |
irisin is controlled by farnesoid x receptor and regulates cholesterol homeostasis. | the aim of this study was to investigate whether the nuclear receptor farnesoid x receptor (fxr) could regulate fndc5/irisin expression and the role of irisin in hyperlipidemia and atherosclerosis in apoe-/- mice. | 2019 | 31191305 |
on the existence of mechanoreceptors within the neurovascular unit of the mammalian brain. | we describe a set of perivascular interneurons (pins) with series of fibro-vesicular complexes (fvcs) throughout the gray matter of the adult rabbit and rat brains. pin-fvcs are ubiquitous throughout the brain vasculature as detected in golgi-impregnated specimens. most pins are small, aspiny cells with short or long (> 1 mm) axons that split and travel along arterial blood vessels. upon ramification, axons form fvcs around the arising vascular branches; then, paired axons run parallel to the ve ... | 2019 | 31190162 |
tumor-targeted 4-1bb agonists for combination with t cell bispecific antibodies as off-the-shelf therapy. | endogenous costimulatory molecules on t cells such as 4-1bb (cd137) can be leveraged for cancer immunotherapy. systemic administration of agonistic anti-4-1bb antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency on fcγ receptor-mediated hyperclustering and hepatotoxicity. to overcome these issues, we engineered proteins simultaneously targeting 4-1bb and a tumor stroma or tumor antigen: fap-4-1bbl (rg7826) and cd19-4- ... | 2019 | 31189721 |
neutralization of rhesus cytomegalovirus il-10 reduces horizontal transmission and alters long-term immunity. | human cytomegalovirus (hcmv) causes severe disease in infants and immunocompromised people. there is no approved hcmv vaccine, and vaccine development strategies are complicated by evidence of both persistent infection and reinfection of people with prior immunity. the greatest emphasis has been placed on reducing transmission to seronegative pregnant women to prevent vertical transmission and its potentially severe sequelae. increasing evidence suggests that the earliest host-hcmv interactions ... | 2019 | 31189602 |
chronically elevated androgen and/or consumption of a western-style diet impairs oocyte quality and granulosa cell function in the nonhuman primate periovulatory follicle. | to investigate the impact of chronically elevated androgens in the presence and absence of an obesogenic diet on oocyte quality in the naturally selected primate periovulatory follicle. | 2019 | 31187329 |
cross-species convergence in pupillary response: understanding human anxiety via non-human primate amygdala lesion. | few studies have used matched affective paradigms to compare humans and non-human primates. in monkeys with amygdala lesions and youth with anxiety disorders, we examined cross-species pupillary responses during a saccade-based, affective attentional capture task. given evidence of enhanced amygdala function in anxiety, we hypothesized that opposite patterns would emerge in lesioned monkeys and anxious participants. a total of 53 unmedicated youths (27 anxious, 26 healthy) and 8 adult male rhesu ... | 2019 | 31184751 |
self-administration of benzodiazepine and cocaine combinations by male and female rhesus monkeys in a choice procedure: role of α1 subunit-containing gabaa receptors. | compounds lacking efficacy at the α1 subunit-containing gabaa (α1gabaa) receptor appear to have reduced abuse potential compared with those having measurable efficacy at this receptor, though their self-administration in nonhuman primates is dependent upon past drug experience. | 2019 | 31183518 |
maternal high-fat diet consumption and chronic hyperandrogenemia are associated with placental dysfunction in female rhesus macaques. | the risk of adverse perinatal outcomes with maternal polycystic ovary syndrome may differ among hyperandrogenic and nonhyperandrogenic phenotypes and is likely modulated by maternal obesity and diet. the relative contribution of maternal hyperandrogenism and nutritional status to placental dysfunction is unknown. female rhesus macaques (n = 39) were assigned at puberty to one of four treatment groups: subcutaneous cholesterol implants and a standard chow diet (controls); testosterone (t) implant ... | 2019 | 31180495 |
convection enhanced delivery of optogenetic adeno-associated viral vector to the cortex of rhesus macaque under guidance of online mri images. | in non-human primate (nhp) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. here, we demonstrate the use of magnetic resonance (mr)-guided convection enhanced delivery (ced) of optogenetic viral vectors into primary somatosensory (s1) and motor (m1) cortices of macaques to obtain efficient, widespread cortical expression of light-sensitive ion channels. adeno-associated viral (aav) vectors encoding the red-shifted opsin c1v1 fused to y ... | 2019 | 31180352 |
genetic diversity and phylogenetic analyses of 11 cohorts of captive rhesus macaques from chinese zoos. | rhesus macaques are raised in almost every chinese zoo due to their likeability and ease in feeding; however, little is yet known about the genetic diversity of rhesus macaques in captivity. in this study, a 475-base pair nucleotide sequence of the mitochondrial dna control region was obtained from the fecal dna of 210 rhesus macaque individuals in captivity. a total of 69 haplotypes were defined, 51 of which (73.9%) were newly identified. of all haplotypes, seven were shared between two zoos, a ... | 2019 | 31179176 |
potential mechanism for hiv-associated depression: upregulation of serotonin transporters in siv-infected macaques detected by 11c-dasb pet. | purpose: increased incidence of depression in hiv+ patients is associated with lower adherence to treatment and increased morbidity/mortality. one possible underlying pathophysiology is serotonergic dysfunction. in this study, we used an animal model of hiv, the siv-infected macaque, to longitudinally image serotonin transporter (sert) expression before and after inoculation, using 11c-dasb (sert ligand) pet imaging. methods: we infected seven rhesus macaques with a neurovirulent siv strain and ... | 2019 | 31178771 |
impact of acute intraocular pressure elevation on the visual acuity of non-human primates. | glaucoma is the leading cause of irreversible blindness worldwide and elevated intraocular pressure (iop) is an established risk factor. visual acuity, the capacity for fine analysis of spatial frequency (sf) information, is relatively preserved in central vision until the later stages of chronic glaucoma. however, for acute glaucoma that is associated with sharp iop elevation, how visual acuity is affected by acute iop elevation remains unclear. | 2019 | 31178426 |
mild hypothermia ameliorates anesthesia toxicity in the neonatal macaque brain. | sedatives and anesthetics can injure the developing brain. they cause apoptosis of neurons and oligodendrocytes, impair synaptic plasticity, inhibit neurogenesis and trigger long-term neurocognitive deficits. the projected vulnerable period in humans extends from the third trimester of pregnancy to the third year of life. despite all concerns, there is no ethically and medically acceptable alternative to the use of sedatives and anesthetics for surgeries and painful interventions. development of ... | 2019 | 31175984 |
once-weekly oral dosing of mk-8591 protects male rhesus macaques from intrarectal challenge with shiv109cp3. | mk-8591 (4'-ethynyl-2-fluoro-2'-deoxyadenosine [efda]) is a novel reverse transcriptase-translocation inhibitor. | 2020 | 31175822 |
synthesis and in vivo evaluation of [18f]ucb-j for pet imaging of synaptic vesicle glycoprotein 2a (sv2a). | synaptic abnormalities have been implicated in a variety of neuropsychiatric disorders, including epilepsy, alzheimer's disease, and schizophrenia. hence, pet imaging of the synaptic vesicle glycoprotein 2a (sv2a) may be a valuable in vivo biomarker for neurologic and psychiatric diseases. we previously developed [11c]ucb-j, a pet radiotracer with high affinity and selectivity toward sv2a; however, the short radioactive half-life (20 min for 11c) places some limitations on its broader applicatio ... | 2019 | 31175396 |
fetal hemoglobin and f-cell variance in mobilized cd34+ cell-transplanted rhesus monkeys. | elevated fetal hemoglobin (hbf) is associated with reduced severity of sickle cell disease. therefore, γ-globin protein levels and f-cell (hbf-positive red blood cell) percentages are used for estimation of clinical benefit. here, we monitored transplantation-related changes in hbf and f-cell percentages for rhesus macaques (macaca mulatta) following total body irradiation or busulfan conditioning prior to cd34+ cell transplantation. hbf protein expression peaked in the first 4-9 weeks posttrans ... | 2019 | 31173819 |
amygdala growth from youth to adulthood in the macaque monkey. | emerging evidence suggests that the human amygdala undergoes extensive growth through adolescence, coinciding with the acquisition of complex socioemotional learning. our objective was to longitudinally map volumetric growth of the nonhuman primate amygdala in a controlled, naturalistic social environment from birth to adulthood. magnetic resonance images were collected at five time-points in 24 male and female rhesus macaques from 6 months to adulthood at 5 years. we then compared amygdala grow ... | 2019 | 31173365 |
cyclic pattern of intraocular pressure (iop) and transient iop fluctuations in nonhuman primates measured with continuous wireless telemetry. | purpose: most studies on intraocular pressure (iop) to monitor iop "fluctuations" in glaucoma patients have been performed with snapshot tonometry techniques that obtain iop measurements at single time points weeks to months apart. however, iop telemetry has shown that iop varies from second-to-second due to blinks, saccades, and systolic vascular filling. the purpose of this study was to characterize the cyclic pattern of baseline iop and transient iop fluctuations in 3 nonhuman primates (nhps) ... | 2019 | 31170817 |
effects of early maternal care on adolescent attention bias to threat in nonhuman primates. | attention bias towards threat using dot-probe tasks has mainly been reported in adults with stress-related disorders such as ptsd and other anxiety disorders, in some cases associated with early life stress or traumatic experiences. studies during adolescence are scarce and inconsistent, which highlights the need to increase our understanding of the developmental processes that predict attentional biases, given that this is a time of emergence of psychopathology. here, we use a translational non ... | 2019 | 31170549 |
potent neutralizing antibodies elicited by dengue vaccine in rhesus macaque target diverse epitopes. | there is still no safe and effective vaccine against dengue virus infection. epidemics of dengue virus infection are increasingly a threat to human health around the world. antibodies generated in response to dengue infection have been shown to impact disease development and effectiveness of dengue vaccine. in this study, we investigated monoclonal antibody responses to an experimental dengue vaccine in rhesus macaques. variable regions of both heavy chain (vh) and light chain (vl) were cloned f ... | 2019 | 31170257 |
post-decision processing in primate prefrontal cortex influences subsequent choices on an auditory decision-making task. | perceptual decisions do not occur in isolation but instead reflect ongoing evaluation and adjustment processes that can affect future decisions. however, the neuronal substrates of these across-decision processes are not well understood, particularly for auditory decisions. we measured and manipulated the activity of choice-selective neurons in the ventrolateral prefrontal cortex (vlpfc) while monkeys made decisions about the frequency content of noisy auditory stimuli. as the decision was being ... | 2019 | 31169495 |
tlr7 agonist administration to siv-infected macaques receiving early initiated cart does not induce plasma viremia. | reduction/elimination of hiv-1 reservoirs that persist despite combination antiretroviral therapy (cart) will likely require induction of viral expression by residual infected cells and enhanced clearance of these cells. tlr7 agonists have potential to mediate these activities. we evaluated immunologic and virologic effects of repeated doses of the tlr7 agonist gs-9620 in siv-infected rhesus macaques receiving cart, which was initiated at 13 days after infection and was continued for 75 weeks pr ... | 2019 | 31167974 |
simian immunodeficiency virus infection modulates cd94+ (klrd1+) nk cells in rhesus macaques. | recently, we and others have shown that natural killer (nk) cells exhibit memory-like recall responses against cytomegalovirus (cmv) and human immunodeficiency/virus simian immunodeficiency virus (hiv/siv) infections. although the mechanism(s) have not been fully delineated, several groups have shown that the activating receptor nkg2c is elevated on nk cells in the context of rhesus cmv (rhcmv) or human cmv (hcmv) infections. cd94, which heterodimerizes with nkg2c is also linked to adaptive nk c ... | 2019 | 31167916 |
viewing heterospecific facial expressions: an eye-tracking study of human and monkey viewers. | common facial expressions of emotion have distinctive patterns of facial muscle movements that are culturally similar among humans, and perceiving these expressions is associated with stereotypical gaze allocation at local facial regions that are characteristic for each expression, such as eyes in angry faces. it is, however, unclear to what extent this 'universality' view can be extended to process heterospecific facial expressions, and how 'social learning' process contributes to heterospecifi ... | 2019 | 31165915 |
brains of rhesus monkeys display aβ deposits and glial pathology while lacking aβ dimers and other alzheimer's pathologies. | cerebral amyloid beta (aβ) deposits are the main early pathology of alzheimer's disease (ad). however, abundant aβ deposits also occur spontaneously in the brains of many healthy people who are free of ad with advancing aging. a crucial unanswered question in ad prevention is why ad does not develop in some elderly people, despite the presence of aβ deposits. the answer may lie in the composition of aβ oligomer isoforms in the aβ deposits of healthy brains, which are different from ad brains. ho ... | 2019 | 31165579 |
reactions to novel objects in monkeys: what does it mean to be neophobic? | animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. in primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. ... | 2019 | 31165297 |
virtual rhesus labyrinth model predicts responses to electrical stimulation delivered by a vestibular prosthesis. | to better understand the spread of prosthetic current in the inner ear and to facilitate design of electrode arrays and stimulation protocols for a vestibular implant system intended to restore sensation after loss of vestibular hair cell function, we created a model of the primate labyrinth. because the geometry of the implanted ear is complex, accurately modeling effects of prosthetic stimuli on vestibular afferent activity required a detailed representation of labyrinthine anatomy. model geom ... | 2019 | 31165284 |
correlation between disease severity and the intestinal microbiome in mycobacterium tuberculosis-infected rhesus macaques. | the factors that determine host susceptibility to tuberculosis (tb) are poorly defined. the microbiota has been identified as a key influence on the nutritional, metabolic, and immunological status of the host, although its role in the pathogenesis of tb is currently unclear. here, we investigated the influence of mycobacterium tuberculosis exposure on the microbiome and conversely the impact of the intestinal microbiome on the outcome of m. tuberculosis exposure in a rhesus macaque model of tub ... | 2019 | 31164469 |
monocyte polarization is altered by total-body irradiation in male rhesus macaques: implications for delayed effects of acute radiation exposure. | radiation-induced fibrosis (rif) is a common delayed effect of acute ionizing radiation exposure (deare) affecting diverse tissues including the heart, lungs, liver and skin, leading to reduced tissue function and increased morbidity. monocytes, which may be classified into classical (cd14++, cd16-), intermediate (cd14++, cd16+) and non-classical (cd14+/low, cd16++) subtypes in humans and non-human primates (nhps), and monocyte-derived macrophages may play an integral role in the pathogenesis of ... | 2019 | 31161966 |
current in vivo models of varicella-zoster virus neurotropism. | varicella-zoster virus (vzv), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. an understanding of vzv neurotropism in humans has long been hampered by the lack of an adequate animal model. for example, experimental inoculation of vzv in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. the severe combined ... | 2019 | 31159224 |
identification of novel rhesus macaque micrornas from naïve whole blood. | micrornas (mirnas) are emerging as novel molecular tools for diagnosing and treating diseases. rhesus monkeys (macaca mulatta) are the most widely used nonhuman primate species for biomedical studies, yet only 912 mature mirnas have been identified in this species compared to 2654 in humans and 1978 in mice. the aim of this project was to help bridge that gap in knowledge by evaluating circulating mirna in naïve rhesus monkeys and comparing results with currently available databases in different ... | 2019 | 31154603 |
safety, toxicity and immunogenicity of a malaria vaccine based on the circumsporozoite protein (fmp013) with the adjuvant army liposome formulation containing qs21 (alfq). | antibodies to circumsporozoite protein (csp) confer protection against controlled human malaria infection (chmi) caused by the parasite plasmodium falciparum. although csp is highly immunogenic, it does not induce long lasting protection and efforts to improve csp-specific immunological memory and duration of protection are underway. we have previously reported that the clinical grade csp vaccine fmp013 was immunogenic and protective against malaria challenge in mice when combined with the army ... | 2019 | 31151801 |
surgical treatment of spontaneous endometriosis in rhesus macaques (macaca mulatta): 11 cases (2007-2011). | objective to determine long-term outcome for rhesus macaques (macaca mulatta) with endometriosis that underwent surgical treatment and identify factors potentially associated with long-term outcome. design retrospective case series. animals 11 female rhesus macaques. procedures medical records of female rhesus macaques in which endometriosis was diagnosed between 2007 and 2011 and that underwent abdominal exploratory surgery were reviewed. results in 5 macaques, the only clinical abnormality was ... | 2019 | 31149880 |
boosting bcg with proteins or rad5 does not enhance protection against tuberculosis in rhesus macaques. | tuberculosis (tb) is the leading cause of death from infection worldwide. the only approved vaccine, bcg, has variable protective efficacy against pulmonary tb, the transmissible form of the disease. therefore, improving this efficacy is an urgent priority. this study assessed whether heterologous prime-boost vaccine regimens in which bcg priming is boosted with either (i) protein and adjuvant (m72 plus as01e or h56 plus caf01) delivered intramuscularly (im), or (ii) replication-defective recomb ... | 2019 | 31149352 |
image correction for diffusion tensor imaging of rhesus monkey thoracic spinal cord. | the relatively tiny spinal cord of non-human primate (nhp) causes increased challenge in diffusion tensor imaging (dti) post-processing. this study aimed to establish a reliable correction strategy applied to clinical dti images of nhp. | 2019 | 31148186 |
simian varicella virus dna in saliva and buccal cells after experimental acute infection in rhesus macaques. | simian varicella virus (svv) infection of non-human primates is the counterpart of varicella zoster virus (vzv) infection in humans. to develop non-invasive methods of assessing svv infection, we tested for the presence of svv dna in saliva, as has been documented in human vzv infection, and in buccal cells to determine whether epithelial cells might provide a more reliable source of material for analysis. five rhesus macaques intratracheally inoculated with svv all developed varicella with vire ... | 2019 | 31143167 |
immunization expands b cells specific to hiv-1 v3 glycan in mice and macaques. | broadly neutralizing monoclonal antibodies protect against infection with hiv-1 in animal models, suggesting that a vaccine that elicits these antibodies would be protective in humans. however, it has not yet been possible to induce adequate serological responses by vaccination. here, to activate b cells that express precursors of broadly neutralizing antibodies within polyclonal repertoires, we developed an immunogen, rc1, that facilitates the recognition of the variable loop 3 (v3)-glycan patc ... | 2019 | 31142836 |
a single substitution in gp41 modulates the neutralization profile of shiv during in vivo adaptation. | the hiv-1 envelope glycoprotein (env) maintains a delicate balance between mediating viral entry and escaping antibody neutralization. adaptation during transmission of neutralization-sensitive envs with an "open" conformation remains poorly understood. by passaging a replication-competent simian-human immunodeficiency virus carrying a highly neutralization-sensitive env (shivcne40) in rhesus macaques, we show that shivcne40 develops enhanced replication kinetics associated with neutralization r ... | 2019 | 31141685 |