After the ABO blood group system, it is the most likely to be involved in transfusion reactions. Results: We quantified A3G and A3F mRNA in PBMC and leukocyte subsets of uninfected and SIVmac-infected rhesus macaques. The module function was identified by dual enrichment. Make a direct impact by volunteering at the annual Tech Challenge! Intracellular cytokine staining (ICS) and immunophenotyping assays were performed using 1 106 PBMC or MNC in R10 medium (described above). 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. In addition, the rhesus serves as a valuable model for studying other human infectious diseases and for vaccine research. Cellular immune responses induced by SARS-CoV-2 challenge were measured in peripheral blood mononuclear cells (PBMCs) using an ex vivo IFN- ELISpot assay and compared to responses measured in uninfected (nave) age and species matched control animals (Fig. Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19. Mononuclear cells, primarily lymphocytes were also noted surrounding and infiltrating the walls of blood vessels (Fig. In the larger airways occasional, focal, epithelial degeneration and sloughing were observed in the bronchial epithelium, with evidence of regeneration, characterised by small, basophilic epithelial cells. Slider with three articles shown per slide. Even now, they are the animals of choice for research into drug addiction and HIV, and roughly two-thirds of all National Institutes of Health-funded primate-related studies use the monkeys. Recent studies have shown that rhesus macaques11,12 and cynomolgus macaques13 can be infected by SARS-CoV-2 and the disease course resembles some features of human COVID-19 infection. Viral load in throat swabs largely mirrored that in nasal washes with peak levels early in infection, although, overall titres were lower. Infection of cells was with ~0.0005 MOI of virus and harvested at day 4 by dissociation of the remaining attached cells by gentle rocking with sterile 5mm borosilicate beads followed by clarification by centrifugation at 1000 g for 10min. But Rh in other species is not exactly the same. Immun. Neutralising virus titres were measured in heat-inactivated (56C for 30min) serum samples. [citation needed], Natural selection aside, the RHD-RHCE region is structurally predisposed to many mutations seen in humans, since the pair arose by gene duplication and remain similar enough for unequal crossing over to occur. Nature 585, 584587 (2020). 9f). wrote the manuscript that was reviewed and accepted by all authors before submission. Dogs can have type A, B, C, D, F, or Tr blood. Nat Med. Sequence reads that mapped to Macaca mulatta or Macaca fascicularis are deposited under NCBI bioproject: PRJNA681111. Protective role of the RhD molecule against Toxoplasma-induced impairment of reaction times in women", "Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study", "Rhnull, the Rarest Blood Type on Earth, Has Been Called the "Golden Blood", "Studies on an agglutinogen (Rh) in human blood reacting with anti-rhesus sera and with human isoantibodies", https://en.wikipedia.org/w/index.php?title=Rh_blood_group_system&oldid=1144239354. J. Other animals with Rh-like antigens causing hemolytic disease of the newborn, Rh disease only occurs in human fetuses however a similar disease called Neonatal isoerythrolysis (NI) can be observed in animal species of newborn horses, mules, pigs, cats, cattle, and dogs. After 5 days incubation at 37C in a humified box, the plates were fixed, stained and plaques counted. Viable virus was successfully recovered from two of the six rhesus macaques and three of the six cynomolgus macaques on the first occasion of sampling (13 dpc). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. In general, there was a trend for spike protein peptide-specific IFN- SFU frequencies measured in PBMC samples collected from cynomolgus macaques to be greater than those detected in rhesus macaques, although these differences did not reach statistical significance. Cell lines were obtained from the European Collection of Authenticated Cell Cultures (ECACC) PHE, Porton Down, UK. The neutralised virus was transferred into the wells of a washed plaque assay 24-well plate (see plaque assay method), allowed to adsorb at 37C for a further hour, and overlaid with plaque assay overlay media. inoculation of a rhesus monkey that results in persistent infection and a histological gastritis similar to that seen in humans 14,15 . The RHAG gene, which is responsible for encoding Rh-associated glycoprotein (RhAG), is found on chromosome 6a. medRxiv https://doi.org/10.1101/2020.04.14.20065771 (2020). In 1940, Karl Landsteiner and Alexander S. Wiener made the connection to their earlier discovery, reporting a serum that also reacted with about 85% of different human red blood cells. Similar to antennas on stereo to catch radio signals, antigens are present on cells to read signals from their environment. Sections were analysed by two qualified veterinary pathologists and peer-reviewed by two other qualified pathologists (veterinary and medical). CD4 T-cell dependent mechanisms of protection have been demonstrated in small animal models of SARS-CoV infection39, T-cells are likely to play an important role in the development of neutralising antibodies40 and the clearance of infection through cell-mediated cytotoxicity32. Peptides were then pooled and aliquoted. "The sequencing of the rhesus macaque genome, combined with the availability of the chimp and human genomes, provides researchers with another powerful tool to advance our understanding of human biology in health and disease," said NHGRI Director Francis S. Collins, M.D., Ph.D. "As we build upon the foundation laid by the Human Genome Project, it has become clear that comparing our genome with the genomes of other organisms is crucial to identifying what makes the human genome unique.". Spike peptide-specific IFN- SFU frequencies measured in mononuclear cells isolated from lung and spleen samples revealed a trend for local cellular immune responses to be greatest in the animals euthanised at the day 14 to19 post-infection time point, but also that there was substantial variability within the groups at this stage of infection (Fig. Representative images from 6 slides per animal at each time point. 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. Liu, X. et al. 16, 284287 (2012). 7). An IFN ELISpot assay was used to estimate the frequency and IFN production capacity of SARS-CoV-2-specific T-cells in PBMCs using a human/simian IFN kit (MabTech, Nacka. Viral RNA was observed in scattered epithelial cells in areas of the upper respiratory tract (nasal cavity, larynx and trachea) of all animals at 4/5 dpc, and not associated with lesions. Bars show median values. When blood from humans was tested with the rabbit serum, the red blood cells of 85% of the humans tested agglutinated (clumped together). To facilitate full examination of the cardiac and pulmonary vasculature, lymph nodes and extrapulmonary tissues, Niopam 300 (Bracco, Milan, Italy), a non-ionic, iodinated contrast medium, was administered intravenously (IV) at 2ml/kg body weight and scans were collected immediately after injection and ninety seconds from the mid-point of injection. The pit of despair was a name used by American comparative psychologist Harry Harlow for a device he designed, technically called a vertical chamber apparatus, that he used in experiments on rhesus macaque monkeys at the University of Wisconsin-Madison in the 1970s. 6a, insert). conceived the study. MJE performed statistical analyses. This work was funded by the Coalition of Epidemic Preparedness Innovations (CEPI) and the Medical Research Council (Project CV220-060, Development of an NHP model of infection and ADE with COVID-19 (SARS-CoV-2). 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. 4f) and airways. The pattern of viral shedding from the URT (peak day one to three with subsequent decline to undetectable), intermittent low recovery from the gastrointestinal tract and the absence of detection above the LLOQ in the blood described across both species is similar to what is observed in humans with asymptomatic/mild COVID-19 (shedding without clinical signs and/or after the resolution of clinical course) and reflect previous reports of SARS-CoV-2 infection in rhesus11,12,18,19 and cynomolgus macaques13,20. Target Ther. PBMC samples were isolated from uninfected animals (nave) or at early (days 4 and 5) and late (days 14-19) time-points following SARS-CoV-2 infection. The rhesus genomic DNA samples used for these studies were contributed by the California NPRC, Oregon NPRC, Southwest NPRC and Yerkes NPRC. Provided by the Springer Nature SharedIt content-sharing initiative. 12, 81 (2021). Anti-c is a common cause of delayed hemolytic transfusion reactions.[15]. Cynomolgus macaques displayed a similar pattern of viral RNA burden in nasal wash samples with peak levels detected at 3 dpc. Pigs can have Ea, Eb, Ga, Ha, and Ka blood. For the Siddharta album, see. Team, R. C. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2019). Lum, F. M. et al. Singh, D. K. et al. 9, 559 (2008). CAS [39][40][41] Before the advent of modern medicine, the carriers of the rarer allele (e.g. Orthologs from Annotation Pipeline: 95 organisms have orthologs with human gene CD1D; Similarly, natural killer cells subsets were identified by expression of CD8, CD159a, CD56 and CD16 within live CD3- lymphocyte subsets. CD1D CD1d molecule [ Macaca mulatta (Rhesus monkey) ] Gene ID: 613268, updated on 16-Aug-2022. CT scans were performed at 18 dpc from the four remaining animals at this time point (Fig. For example, the rhesus monkey Tetra, born in 2000, was the first cloned primate. He covers all things human origins and astronomy as well as physics, animals and general science topics. In addition, samples were stained using the RNAscope technique to identify the SARS-CoV-2 virus RNA. (1963) suggested that high R0 frequencies were likely characteristic of the ancient Judea Jews, who had emigrated from Egypt prior to their dispersal throughout the Mediterranean Basin and Europe[7] on the basis of high R0 percentages among Sephardi and Ashkenazi Jews compared to native European populations and the relative genetic isolation of Ashkenazim. The CD1D gene is conserved in human, chimpanzee, cow, mouse, and rat. These individuals, if alloimmunized to D, can produce an anti-D antibody. performed the bioinformatic data analysis. "Individuals who self-identify as white will respond in diverse ways to genetic testing showing that they have recent African ancestry," said Saunt. 133, 2032 (2008). Wiener's notation is more complex and cumbersome for routine use. Prior to challenge animals were housed at Advisory Committee on Dangerous Pathogens (ACDP) level two in cages approximately 2.5M high by 4M long by 2M deep, constructed with high level observation balconies and with a floor of deep litter to allow foraging. Juno, J. After trimming, reads shorter than 10bp were removed. No name was given to this agglutinin when described. Mononuclear cells (MNC) were isolated from spleen and lung tissue samples using an OctoMACS tissue dissociation device (Miltenyi Biotec). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in A probable genotype may be speculated on, based upon the statistical distributions of genotypes in the patient's place of origin. RNA was isolated from nasal wash, throat swabs, EDTA treated whole blood, BAL and tissue samples (nasal cavity, tonsil, trachea and lung). a, b IFN SFU measured in PBMCs and stimulated with spike protein peptide pools (PP) peptide in (a) rhesus and (b) cynomolgus macaques. Rockx, B. et al. Appropriate positive and negative controls were included in each RNAscope run (Supplementary Fig. Moreover, cynomolgus macaques with a Mauritian genotype have more restricted genetic variability and more limited and better-defined MHC, providing an advantage in the battle to elucidate correlates of protective immunity. 8, 475481 (2020). Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non- human primates. Intracellular antigen staining was applied by incubation at room temperature for 30min with the antibodies CD3-AF700, IFN--PeCy7, TNF--BUV395, GM-SCF-PE (all from BD Biosciences, Oxford, United Kingdom), IL-2-APC (Miltenyi Biotech Ltd), IL-17-BV711 (Biolegend, London, UK) prepared in brilliant stain buffer. [45] Only 43 individuals have been reported to have it worldwide. That tradition is waning, but it is, unfortunately, far from extinguished. Bars indicating group meanstandard error with PRNT50 determined for individual animals shown as circles and squares respectively. Lung: early rhesus n=2, late rhesus n=3, early cyno n=2, late cyno n=2. kn Intracellular cytokine staining data. The Wiener system used the RhHr nomenclature. J. Virol. Rotation speed was 0.8s. Images were displayed as an 11cm field of view. 1). These terms do not indicate which specific antigen-antibody incompatibility is implicated. On the other hand, Wiener's theory that there is only one gene has proved to be incorrect, as has the FisherRace theory that there are three genes, rather than the 2. ", "Distribution of Rhesus blood group antigens and weak D alleles in the population of Albania", "High rhesus (Rh(D)) negative frequency and ethnic-group based ABO blood group distribution in Ethiopia", "Prevalence of weak D phenotype among D negative C/E+ blood donors in Morocco", "It is worthwhile filling in the remaining blank spots for blood group antigen frequencies", "Distribution of ABO and Rh-D blood groups in the Benin area of Niger-Delta: Implication for regional blood transfusion", "Distribution of ABO and Rhesus (RHD) Blood Groups in Al-Jouf Province of the Saudi Arabia", "RHCE represents the ancestral RH position, while RHD is the duplicated gene", "Function of human Rh based on structure of RhCG at 2.1 A", "The structure and function of the Rh antigen complex", "Neurophysiological effect of the Rh factor. https://doi.org/10.5694/mja2.50569 (2020). These histopathological lesions are compatible to those observed in human patients, although some features seen in humans, such as thromboembolic changes, were not present in the macaques29. And in other parts of the South, it was about 1 in 10. For SARS-CoV-1, though rhesus macaques became the preferred species, yet the literature suggests there is no significant difference in susceptibility of cynomolgus (Macaca fascicularis) or rhesus macaques (Macaca mulatta) to infection, virus replication and pathology7,8,9,10. Simply put, the weak D phenotype is due to a reduced number of D antigens on a red blood cell. As can be seen in the table below, most of the Rh phenotypes can be produced by several different Rh genotypes. The cut-off was set at the average Optical Density of samples collected from nave animals (Day 0) + 3 Standard Deviation. This is consistent with the same mysterious rearrangements seen in the human lineage's X chromosome following the branching off of the chimpanzee, and gives "us new evidence of the unusual role of this sex chromosome in primate evolution," said researcher Aleks Milosavljevic at the Baylor College of Medicine. and M.J.D. This real factor found in rhesus macaque was classified in the Landsteiner-Weiner antigen system (antigen LW, antibody anti-LW) in honor of the discoverers.[53][54]. 9d). This page was last edited on 12 March 2023, at 16:24. Rowe, T. et al. Abnormalities occurred in the peripheral two thirds of the middle and lower lung lobes in the two cynomolgus macaques and in a random pattern in the upper, middle and lower lobes of the rhesus macaque. and N.W. 4e). "We needed many, many people," said lead study author Kasia Bryc, "so it wasn't possible just a short time ago. In rhesus macaques, the IFN- SFU measured following stimulation with spike protein peptide megapools (MP) 13 did not differ significantly between animals euthanised at either the day 45 (early) or the day 1419 (late) post-infection time-point in comparison to SFU frequencies measured in the nave control animals. During the 1950s, they were the laboratory animal models used to investigate, develop, and produce the polio vaccine ( Johnsen, 1995 ). Due to their obvious physiological similarities to humans, non-human primates (NHPs), such as macaques, have long been recognised as the most clinically relevant animal for the development of in vivo models of human disease. The name rhesus factor (Rh) goes back to the use of erythrocytes extracted from the blood of rhesus monkeys for obtaining the first blood serum. 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. 6i) at 14/15 dpc, with no significant expression observed at 18/19 dpc. The others are much less frequently encountered or are rarely clinically significant. Rhnull individuals have no Rh antigens (no Rh or RhAG) on their red blood cells. [17] The Rh proteins in other species, however, do not correspond with the Rh blood group or antigens found on human red blood cells. These results were in line with the viral subgenomic RNA (sgRNA) that was greatest for rhesus macaques at 2 dpc and cynomolgus macaques at 3 dpc (Fig. Although differences between these two sera were shown already in 1942 and clearly demonstrated in 1963, the already widely used term "Rh" was kept for the clinically described human antibodies which are different from the ones related to the rhesus monkey. Low levels of neutralising antibody were detected by plaque reduction neutralisation test (PRNT) assay in both cynomolgus and rhesus macaques for the first 89 days post-challenge. [15][43], The first Rhnull blood was discovered in an Aboriginal Australian woman, in 1961. Join us for Silicon Valley's most inspiring weekend! Four companion papers that relied on the rhesus sequence also appear in the same issue. Some keystones were to recognize its importance for blood transfusion (including reliable diagnostic tests), hemolytic disease of the newborn (including exchange transfusion), and very importantly the prevention of it by screening and prophylaxis. Expression observed at 18/19 dpc to antennas on stereo to catch radio signals, antigens present! And Ka blood have type a, B, C, D, F, Tr. A humified box, the first rhnull blood was discovered in an Aboriginal Australian woman in! Collected from nave animals ( Day 0 ) + 3 Standard Deviation first blood. 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