The rhesus monkey (Macaca mulatta), an Old World Monkey species widely used for biomedical research, is an ideal choice, due to its high sequence similarity with humans (>93% for protein-coding genes) and yet relatively large phylogenetic distance (about 25 million years of divergence from humans), which alleviates ethical concerns . Even before DNA analysis, families repudiated relatives they knew were theirs. Ten peptide pools were used, comprising of 15mer peptides, overlapping by 11 amino acids and offset by 4 amino acids. Horses have groups A, C, D, K, P, Q, and U. Following surface marker staining, the cells were washed and then permeabilised by incubation at room temperature for 15min with Fix/Perm reagent (BD Biosciences) before washing with Permwash buffer (BD Biosciences). In distal bronchioles, degeneration and sloughing of epithelial cells were present, with areas of attenuation; in alveolar walls associated with bronchiolo-alveolar junctions, foci of plump, type II pneumocytes were noted, representing regeneration. Given the limitations in reproducing the range of underlying health conditions in humans that link to poorer infection outcomes (e.g. The antigen that induced this immunization was designated by them as Rh factor to indicate that rhesu s blood had been used for the production of the serum. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The hemolytic condition occurs when there is an incompatibility between the blood types of the mother and fetus. Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys. Non-tissue samples were inactivated in AVL (Qiagen) and ethanol, with final extraction using the QIAamp Viral RNA Minikit (Qiagen) as per manufacturers instructions. Polyfunctional cells were identified using Boolean gating combinations of individual cytokine-producing CD4 or CD8 T-cells. A functional polymorphism in the promoter region of the serotonin transporter (5-HTT) gene was found to moderate the influence of stressful life events on depression. We perform sequential body fluid sampling and culls (at days 4/5, 14/15 and 18/19) to support a comprehensive comparative assessment of clinical signs, pathology, virology and immunology. 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The new analysis of the rhesus monkey genome, conducted by an international consortium of more than 170 scientists, also reveals that humans and the macaques share about 93 percent of their DNA. The testing is difficult, since using different anti-D reagents, especially the older polyclonal reagents, may give different results. In the lumen of some airways, mucus admixed with degenerative cells, mainly neutrophils and epithelial cells, was seen. [42]:324, Some of the other Rh "antigens" are f ("ce", RH6), Ce (RH7), Cw (RH8), Cx (RH9), V (RH10), Ew (RH11), G (RH12), Tar (RH40), VS (RH20), Dw (RH23), and CE (RH22). Did we get it from Rhesus monkeys? Additional environmental enrichment was afforded by the provision of toys, swings, feeding puzzles and DVDs for visual stimulation. PBMCs and MNC were thawed, washed in R10 medium (consisting of RPMI 1640 supplemented with 2 mM L-glutamine, 50 U/ml penicillin- 50g/ml streptomycin, and 10% heat-inactivated FBS) with 1 U/ml of DNase (Sigma), and resuspended in R10 medium and incubated at 37C 5% CO2 overnight. Arrows in images (a1), (b1) and (c1) indicate areas of peripheral ground glass opacification. [52] In May 1941, the third anti-Rh serum (M.S.) Cynomolgus macaques nave vs PP9 p=0.03, nave vs MP2 p=0.03, nave vs MP3 p=0.01, nave vs summed p=0.01. The Rh blood group system consists of 49 defined blood group antigens,[1] among which the five antigens D, C, c, E, and e are the most important. However, levels later in infection remained higher with titres of 2.0 106 cDNA copies/ml at 15 dpc and 1.6 105 cDNA copies/ml at 19 dpc (Fig. Oklahoma, the study revealed, has the highest proportion of self-identified African-Americans with Native American genes. Download Datasets Summary. Using the subjective histopathology scoring system, scores were higher in both macaque species at 4/5 dpc compared to 14/15 and 18/19 dpc, mostly due to higher scores in the alveolar damage parameters observed at the early time point (Fig. Huang, C. et al. March 22, 2023 . Images from CT scans collected 18 days after challenge from two rhesus and two cynomolgus macaques, were examined by an expert thoracic radiologist with prior experience of non-human primate CT interpretation and human COVID-19 CT features, blinded to the clinical status. In general, CD69 expression on CD4, CD8 and T-cell populations was higher at the later post-infection timepoints (Fig. Sequences of primers and probes are included in Supplementary Table1. Cell lines were obtained from the European Collection of Authenticated Cell Cultures (ECACC) PHE, Porton Down, UK. The resultant Sam files were processed by featureCounts v2.0.057 with the default setting to generate raw read counts per gene. Features characteristic of COVID-19 in human patients, such as ground glass opacity and consolidation were identified on CT scans collected from both SARS-CoV-2 challenged rhesus and cynomolgus macaques in line with reports from studies describing SARS-CoV-2 infection in either, rhesus24, or cynomolgus macaques20 supporting a role for both species as models of human SARS-CoV-2 induced disease. This comparative data is reiterated in the global transcriptomics response between the two species that closely resemble a mild to moderate COVID-19 in humans. Overall, alveolar necrosis was a prominent feature in the affected areas, characterised by individual, shrunken, eosinophilic cells in alveolar walls, with pyknotic or karyorrhectic nuclei (Fig. [citation needed], The proteins which carry the Rh antigens are transmembrane proteins, whose structure suggest that they are ion channels. What differs between Rh disease and NI is the pathogenesis of hemolysis between human fetuses and the animal species. Gating strategy for flow cytometry analyses are summarised in Supplementary Figs. Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non- human primates. bioRxiv https://doi.org/10.1101/2020.06.05.136481 (2020). 6h) and rhesus macaques (Fig. Typically, Rhesus positive people have an intact RHD gene while negative people lack the gene (or have mutations in it). 5, 6. 5, 157 (2020). Chicago, ASCP Press, 2009. hemolytic disease of the fetus and newborn, "dbRBC Blood Group Antigen Gene Mutation Database", "RHD Rh blood group, D antigen [Homo sapiens] Gene Result", "RHCE Rh blood group, CcEe antigens [Homo sapiens] Gene Result", "The effects of altitudinal variation in Ethiopian populations", "A genetic study of nine populations from the region of Tlemcen in Western Algeria: a comparative analysis on the Mediterranean scale", "The Rh allele frequencies in Gaza city in Palestine", "Sequence diversity of the Rh blood group system in Basques", "The Rh chromosome frequencies in England", "Rh Subgroups and Kell Antigens in Patients With Thalassemia and in Donors in Turkey", "CeRh1 (rhr-1) is a dominant Rhesus gene essential for embryonic development and hypodermal function in Caenorhabditis elegans", "What is Rhesus factor? For example, this approach has been used to analyse blood samples to differentiate patients with acute Ebola virus disease who went on to survive or die16 or to characterise Zika virus infection in the placenta during different trimesters17. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Viral load in throat swabs largely mirrored that in nasal washes with peak levels early in infection, although, overall titres were lower. 17, 533535 (2020). NEW YORK - A team of researchers from around the US has developed an updated reference genome assembly of the rhesus macaque (Macaca mulatta) the most widely used nonhuman primate (NHP) model in biomedical research finding new lineage-specific genes and expanded gene families that could be informative in studies of evolution and human disease. In this case, RNAseq was used to identify and quantify mRNA in blood samples taken longitudinally during infection. In addition to the above functional parameters, antigen-specific expression of the activation marker CD69 was assessed to provide a measure of the overall activation status and SARS-CoV-2 antigen-reactogenicity of T-cell subsets following infection. [48] The serum that led to the discovery was produced by immunizing rabbits with red blood cells from a rhesus macaque. Rh and Amt dont just share DNA sequence: they also have similar jobs! Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia. Cite this article. Rh(D) status of an individual is normally described with a positive (+) or negative () suffix after the ABO type (e.g., someone who is A+ has the A antigen and Rh(D) antigen, whereas someone who is A has the A antigen but lacks the Rh(D) antigen). This included the detection of antigen-specific immune responses directed toward peptide-epitopes spanning the S protein sequence, an antigen incorporated into several of the novel vaccine candidates currently under investigation41, thus demonstrating the value of the macaque model for immunogenicity testing of novel SARS-CoV-2 vaccine candidates. Since Amt is found in really ancient lifeforms like Archaea, we know that Rh must have evolved from that more ancient protein. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Miles W. Carroll. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Phorbol 12-myristate (Sigma) (100ng/ml) and ionomycin (CN Biosciences, Nottingham, UK) (1mg/ml) were used as a positive control. Interrogation of IFN- spot forming units (SFU) measured in response to stimulation with overlapping 15-mer spike protein-peptide pools indicated that peptides spanning the breadth of the SARS-CoV-2 spike protein sequence induced cellular immune responses in infected cynomolgus macaques; whereas, peptide pool (PP) sequences 2-4 and 8 were most immunogenic in rhesus macaques (Fig. The annual event is back in person! X.D. Similarly, cytokine production measured in the T-cell population indicated a trend for greater IL-17 production in PBMCs isolated from rhesus macaques, although low frequencies of IFN- and IL-17 producing T-cells were also detected in cynomolgus macaques euthanised at the early post-infection time point indicating that unconventional T-cell populations play a role in the early immune response to SARS-CoV-2 infection (Fig. [10] On the contrary, at a frequency of 47.2% of the population of Basque country having the lack of the D antigen, these people display the highest frequency of the Rh negative phenotype. Biologically independent animal samples for (ad); PBMCs: nave n=6, early n=2, late n=4 Biologically independent animal samples for (e); lung and spleen: early n=2, late n=4, (fj) Frequency of major lymphocyte and monocyte cell populations quantified by immunophenotyping assay (fh) CD4+, CD8+ and T-cell frequencies in PBMCs and lung cells, (i) Monocyte subtype frequency in PBMCs and lung MNCs, (j) Natural killer (NK) cell subset frequency in PBMCs and lung MNCs. "That would be an amazing feat. We compare the transcriptomes of three biological replicates of ORMES6 (A, B and C) with pooled differentiated EBs to identify 367 rhesus monkey putative stemness genes. 3b). Viral RNA was detected in the nasal cavity, lung and trachea early in infection at 4 and 5 dpc. We decided to use the lentivirus above-mentioned in a previous described approach [ 2] of infecting early-cleavage-stage embryos ( Fig. And to have Rhesus blood type, your red blood cells should have Rh antigens. 6f) and rhesus macaques (Fig. The percentage of alloimmunization is significantly reduced in patients who are actively exsanguinating.[14]. In addition, samples were stained using the RNAscope technique to identify the SARS-CoV-2 virus RNA or Interleukin 6 (IL-6) in lung tissue sections. Virus was not recovered from any nasal wash samples collected from 4 dpc onwards. Analysis of Rhesus Monkey Genome Uncovers Genetic Differences With Humans, Chimps DNA Comparison Provides New Clues to Primate Biology. Only customers who said they identified with a single racial or ethnic group were included. F.J.S., A.D.W., M.J.D., S.S., J.A.H. CT provided the only clinical measure that identified abnormalities in vivo consistent with COVID-19 and is therefore a critical tool for evaluation of disease burden following experimental infection. Rhesus factor is a part of your blood type. Previously, rhesus macaques were inoculated with the macaque When receiving blood, they are sometimes typed as a "D negative", though this is the subject of some debate. Nature 581, 465469 (2020). Anti-c is a common cause of delayed hemolytic transfusion reactions.[15]. bioRxiv https://doi.org/10.1101/2020.05.13.093195 (2020). and M.W.C. In rhesus macaques, viral RNA was detected in one animal at 3 dpc, whilst in cynomolgus macaques, viral RNA was detected in two animals at 6 dpc. 9m, n). J. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to assess the safety and efficacy of novel vaccines and therapeutics. Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study. clusterProfiler: an R package for comparing biological themes among gene clusters. Bars show median values. Charles has visited every continent on Earth, drinking rancid yak butter tea in Lhasa, snorkeling with sea lions in the Galapagos and even climbing an iceberg in Antarctica. Macroscopic changes, considered to be associated with infection, were not observed in any other organ analysed in this study at any time point. These include genes involved in hair formation, immune response, membrane proteins and sperm-egg fusion. One-to-one orthologs were defined as the orthologous genes of M. mulatta and M. fascicularis in Ensembl (release-94) with reciprocally highest homologue ortholog confidence. This was previously referred to as Du, which has been replaced. The sample size used in this study is relatively limited (6 rhesus and 6 cynomolgus macaques), and therefore, there are limitations to provide statistical significance for some endpoints. J. Clin. The cut-off was set at the average Optical Density of samples collected from nave animals (Day 0) + 3 Standard Deviation. Whole-genome sequencing of the viral challenge stock, used in this study (Passage 3), confirmed there were no significant changes following passage in Vero/hSLAM cells, compared to the original isolate (Passage 1). ISH detection of abundant viral RNA (RNAScope, red chromogen) within the areas of pneumonia (a, arrows) and occasionally in the BALT (a, insert, arrow) in cynomolgus (a, b) and rhesus macaques (b, arrows) at 4/5 dpc. Following incubation, cells were washed with FACS buffer consisting of PBS+1% FCS and incubated for 30min at room temperature with optimal dilutions of the amine-reactive Live/Dead Fixable Red viability cell stain (Life Technologies) and the antibodies CD4 PerCP-Cy5.5, CD8 APC-Fire750, CD69-BV510, (all from BD Biosciences) and CD20- Pe-Dazzle-594, -TCR-BV421 (Biolegend, London, UK) prepared in BD Biosciences Brilliant stain buffer (BD Biosciences, Oxford, UK). rhesus monkey: [noun] a pale brown Asian macaque (Macaca mulatta) often used in medical research — called also#R##N# rhesus, rhesus macaque. Rev. Each is given a number, though the highest assigned number (CEVF or RH61 according to the ISBT terminology) is not an accurate reflection of the antigens encountered since many (e.g. Images constructed from CT scans collected 18 days after challenge with SARS-CoV-2 showing pulmonary abnormalities in two cynomolgus (a, b) and one rhesus macaque (c). Google Scholar. 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Wash samples collected from 4 dpc onwards CD8 and rhesus monkey gene in caucasian populations was at. The older polyclonal reagents, especially the older polyclonal reagents, may different. The percentage of alloimmunization is significantly reduced in patients who are actively exsanguinating. [ 14 ] previously. Antigens are transmembrane proteins, whose structure suggest that they are ion.! Of alloimmunization is significantly reduced in patients who are actively exsanguinating. [ 14 ] analyses are summarised Supplementary!