Human and chimp DNA is so similar because the two species are so closely related. In this respect, genotyping of blood groups has much simplified this detection of the various variants in the Rh blood group system. For IL-6 mRNA, the areas of histopathological lesions were selected as regions of interest (ROI) and the positively labelled area (red) was calculated by the software after setting the thresholds. Inoculum (5 106 PFU) was delivered by intratracheal route (2ml) and intranasal instillation (1.0ml total, 0.5ml per nostril). Animals were monitored for clinical signs and blood/swab/tissue samples were taken for virology, immunology and pathology. 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. The scans showed the expected distribution of [ 11 C]CFN corresponding to the known mu opioid receptor density in the primate brain, with pronounced uptake in the basal ganglia (BG) and thalamus (THAL), as well as moderate uptake throughout the . Johnson, R. M., Dahlgren, L., Siegfried, B. D. & Ellis, M. D. Acaricide, fungicide and drug interactions in honey bees (Apis mellifera). Following the manufactures protocols, total RNA was used as input material into the QIAseq FastSelectrRNA HMR (Qiagen) protocol to remove cytoplasmic and mitochondrial rRNA with a fragmentation time of 7 or 15min. van Doremalen, N. et al. Lancet 361, 13121313 (2003). 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). 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. Whole-genome sequencing was performed, on the P3 challenge stock, using both Nanopore and Illumina as described previously47. Each library was quantified using Qubit and the size distribution assessed using the Agilent 2100 Bioanalyser and the final libraries were pooled in equimolar ratios. There will be a few changes, which cause the Rh molecules of those animals to be slightly different from yours. Wiener's notation is more complex and cumbersome for routine use. and T.T. After incubation at 37C for 120h, they were fixed overnight with 10% (w/v) formalin/PBS, washed with tap water and stained with methyl crystal violet solution (0.2% v/v in 40% (v/v) Ethanol) (Sigma). The newborn animal is without NI but soon develops hemolytic anemia after initial ingestion of its mothers colostrum that contain antibodies that can be absorbed through the newborns intestines and are incompatible to its red blood cell antigen. rhesus monkey gene in caucasian. Cells 1, 514 (2012). A.D.W., L.S., C.S., S.Lo., O.D.-P., K.G., A.M., A.L.M. Learn to do research before embarrassing yourself." Humans NOT hybridized with the Annunaki have 2 Rhesus-monkey genes, giving 100% chance of Rh-positive blood. 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. Proinflammatory (IFN- or GM-CSF producing) T-cells were primarily detected at the later post-challenge time point, although low frequencies of IL-2 producing CD8+ cells were detected in PBMC samples collected from cynomolgus macaques in the early post-challenge samples (Fig. Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys. Before use peptides were resuspended to a concentration of 5g/peptide in media, they were then loaded onto the ELISpot plate, 50l/well. At 14/15 and 18/19 dpc, only small areas of consolidation were observed. 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. In their analysis, scientists from 35 institutions compared this melded assembly to the reference sequence of the human genome, a newer unpublished draft sequence of the chimp genome, the sequence of more than a dozen other more distant species already in the public databases, the human HapMap, and the Human Gene Mutation Database that lists known human mutations that lead to genetic disease. Virus was not recovered from any nasal wash samples collected from 4 dpc onwards. [18], According to a comprehensive study, the worldwide frequency of Rh-positive and Rh-negative blood types is approximately 94% and 6%, respectively. 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 addition, Vero/hSLAM cultures were supplemented with 0.4mg/ml of geneticin (Invitrogen) to maintain the expression plasmid. In rhesus macaques, viral RNA in nasal washes peaked at 2 dpc at 6.92.3 107 cDNA copies/ml and levels remained between 2.9 105 and 4.8 107 cDNA copies/ml until 11 dpc, before decreasing to 1.8 104 cDNA copies/ml by 18 dpc. For instance, the monkey's X chromosome showed an unexpectedly large number of times in which its parts got shuffled around. 6, eaba8399 (2020). ADS Stacked bars show the group median with 95% confidence intervals. 212, 459462 (2020). This was most notable at 2 dpc (Fig. Serum neutralisation titres as reciprocal highest dilution resulting in an infection reduction of >50% in samples (PRNT50) pre-challenge and at 13, 46, 89, 1112 and 1419 days post-challenge in rhesus macaques (blue) and cynomolgus macaques (red). Pulmonary emboli were not identified in any of the subjects. Crossref Medline Google Scholar; 5 Tarantal AF, Lee CCI, Jimenez DF, Cherry SR. Fetal gene transfer using lentiviral vectors: in vivo detection of gene . Monocyte subtypes were characterised as classical, non-classical or intermediate by expression of CD14+ and CD16+. Lewandowski, K. et al. Cytokine-producing T-cells were identified using a forward scatter-height (FSC-H) versus side scatter-area (SSC-A) dot plot to identify the lymphocyte population, to which appropriate gating strategies were applied to exclude doublet events, non-viable cells and B cells (CD20+). In the cynomolgus macaques, patchy infiltration of mainly mononuclear cells in the alveolar walls, with occasional similar cells within alveolar spaces, and parenchymal collapse, were seen (Fig. All Rh antibodies except D display dosage (antibody reacts more strongly with red cells homozygous for an antigen than cells heterozygous for the antigen (EE stronger reaction vs Ee). [49], In 1939, Phillip Levine and Rufus Stetson published in a first case report the clinical consequences of non-recognized Rh factor, hemolytic transfusion reaction, and hemolytic disease of the newborn in its most severe form. The polypeptides produced from the RHD and RHCE genes form a complex on the red blood cell membrane with the Rh-associated glycoprotein. Like in humans, blood groups in animals vary by region. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed using TaqPath 1-Step RT-qPCR Master Mix, CG (Applied Biosystems), 2019-nCoV CDC RUO Kit (Integrated DNA Technologies) and 7500 Fast Real-Time PCR System (Applied Biosystems) as previously described48. Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. e1003. Regarding patient treatment, only the phenotype is usually of any clinical significance to ensure a patient is not exposed to an antigen they are likely to develop antibodies against. Robinson, M. D., McCarthy, D. J. Additional information about NHGRI can be found at its Web site, www.genome.gov. Join us for Silicon Valley's most inspiring weekend! 4d). The Tech Interactive201 S. Market St.San Jose, CA 95113. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. 23andMe was the first source that could offer this kind of data.". This means that important features that have been conserved in primates over time can be more easily seen by comparing rhesus to human, than chimp to human. Pathological changes consistent with those described for cynomolgus macaques were present in the lungs of rhesus macaques. This is important, since most blood banks have a limited supply of "D negative" blood and the correct transfusion is clinically relevant. Images from a second rhesus macaque did not have abnormal features. These individuals, if alloimmunized to D, can produce an anti-D antibody. I.e., the response occurred at the start of infection and then wanes with length of infection. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2, Establishment of an African green monkey model for COVID-19 and protection against re-infection, Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes, Comparison of nonhuman primates identified the suitable model for COVID-19, Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets, Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques, Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates, SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801, https://www.ncbi.nlm.nih.gov/bioproject/PRJNA681111, https://www.who.int/publications/m/item/weekly-epidemiological-update---24-november-2020, https://doi.org/10.1038/s41586-020-2324-7, https://doi.org/10.1101/2020.06.05.136481, https://doi.org/10.1101/2020.05.13.093195, https://doi.org/10.1016/S1470-2045(20)30309-0, https://doi.org/10.1016/S1473-3099(20)30434-5, https://doi.org/10.1016/j.jaci.2020.05.008, https://doi.org/10.1101/2020.04.14.20065771, https://doi.org/10.1038/s41591-020-0995-0, https://www.theatlantic.com/science/archive/2020/08/america-facing-monkey-shortage/615799/, https://doi.org/10.1002/0471142735.im1214s102, https://www.nc3rs.org.uk/non-human-primate-accommodation-care-and-use, https://doi.org/10.1038/s41591-020-0913-5, http://creativecommons.org/licenses/by/4.0/, Monitoring and immunogenicity of SARS-CoV-2 vaccination of laboratory rhesus monkeys (Macaca mulatta), A low dose of RBD and TLR7/8 agonist displayed on influenza virosome particles protects rhesus macaque against SARS-CoV-2 challenge, The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection, Long-read assembly of major histocompatibility complex and killer cell immunoglobulin-like receptor genome regions in cynomolgus macaque, Identification and characterization of the T cell receptor (TCR) repertoire of the cynomolgus macaque (Macaca Fascicularis), Sign up for Nature Briefing: Translational Research. Box plots show the group median+/ inter-quartile range, with minimum and maximum values connected by whiskers. Genome Biol. Miles W. Carroll. 133, 2032 (2008). 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. Lancet Respir. When blood from humans was tested with the rabbit serum, the red blood cells of 85% of the humans tested agglutinated (clumped together). [16], Rh molecules can be found in many different living organisms from worms, bacteria, algae, and other vertebrates. Cells were stimulated overnight with SARS-CoV-2 peptide pools and megapools of the spike protein (Mimotopes, Australia). After washing, 1mg/ml O-phenylenediamine dihydrochloride solution (Sigma) was prepared and 100l per well were added. A team of scientists from the U.S. and China created a mixed embryo with human stem cells and macaque monkey cells. 2A ). The Wiener system used the RhHr nomenclature. [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). NY 10036. F.J.S., L.H., C.L.K., G.P., E.L.R. There are other posts on this site that talk about the basics of Rhesus factor, so here I will talk more about the evolution of Rhesus factor, and blood type in animals. In the same way that DNA has instructions for what you might look like, it also has instructions for how your molecules get made. The practical implication of this is that people with this sub-phenotype will have a product labeled as "D positive" when donating blood. The published data suggested that only the protection of RhD-positive heterozygotes was long term in nature; the protection of RhD-positive homozygotes decreased with duration of the infection while the performance of RhD-negative homozygotes decreased immediately after the infection. Animal models and vaccines for SARS-CoV infection. Positive mononuclear cells were also observed rarely in the bronchus-associated lymphoid tissue (BALT) (Fig. A lung histopathology scoring system was setup and used to evaluate the severity of the histopathological lesions observed in each animal (Table1), including lesions affecting the airways and the parenchyma. 16, 284287 (2012). PCR amplicons were quantified against 2019-nCoV_N_Positive Control (Integrated DNA Technologies). datasets were normalised and log-transformed with the command rpkm() in EdgeR58. Did we get it from Rhesus monkeys? Remarkable changes were not observed in any other tissue. As much as 12% of self-described European Americans from South Carolina and Louisiana had African ancestry. Compared with uninfected animals, we found increased A3G and A3F mRNA levels in PBMC, purified CD4+ T-cells and CD14+ monocytes as well as lymph node cells from asymptomatic SIV-infected macaques. Front Immunol. Only customers who said they identified with a single racial or ethnic group were included. Our findings confirm that proinflammatory and cytotoxic T-cells are induced by SARS-CoV-2 infection in both rhesus and cynomolgus macaques to a similar extent, and that there is T-cell reactogenicity in both species to all three of the SARS-CoV-2 antigens included in our assays. For more information about NIH and its programs, visit www.nih.gov. About the National Institutes of Health (NIH): JAMA https://doi.org/10.1001/jama.2020.4326 (2020). Subsequently, the NEBNext Ultra II Directional RNA Library Prep Kit for Illumina (New England Biolabs) was used to generate the RNA libraries, followed by 11 or 13 cycles of amplification and purification using AMPure XP beads. https://doi.org/10.1038/s41467-021-21389-9, DOI: https://doi.org/10.1038/s41467-021-21389-9. rhesus monkey gene in caucasian. Rhesus macaques (Macaca mulatta) are sandy-furred, pink-faced monkeys that live in the region ranging from Afghanistan to northern India, as well as southern China, and are traditionally held as sacred in Hinduism. Vabret, N. et al. Construction and characterization of rhesus monkey rotavirus (MMU18006)- or bovine rotavirus (UK)-based serotype G5, G8, G9 or G10 single VP7 gene substitution reassortant candidate vaccines . Hisat2 v2.1.056 was used to map the trimmed reads on the Macaca mulatta or Macaca fascicularis reference host genome assemblies (release-94) downloaded from the Ensembl FTP site. 3c). Animals were euthanised at 3 different time-points, in groups of four (including one animal from each species and sex) at 4/5, 14/15 and 18/19 dpc (Fig. 3e). Uniquely, our conclusion that these two species respond similarly to SARS-CoV-2 infection, is supported by our transcriptional analysis which provides a global view on host gene expression. 6c, d). NC3RS https://www.nc3rs.org.uk/non-human-primate-accommodation-care-and-use (2017). Emerg. "We needed many, many people," said lead study author Kasia Bryc, "so it wasn't possible just a short time ago. 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. Weighed tissue samples were homogenised and inactivated in RLT (Qiagen) supplemented with 1%(v/v) Beta-mercaptoethanol. G.S.S., K.E.G., H.E.H., R.J.W., L.A., E.B., K.R.Bu., M.A., N.S.C., D.K., K.J.G., J.G., R.H., S.Le., E.J.P., S.P., C.T. When you do this, you find that other animals have very similar Rh! Callaway, E., Cyranoski, D., Mallapaty, S., Stoye, E. & Tollefson, J. Because this worm does not have red blood cells, it cannot have Rh antigens, excluding it from having a Rh blood type. 1). Study groups comprised three males and three females of each species and all were adults aged 24 years and weighing between 2.89 and 4.85kg at time of challenge. Importance of blood groups and blood group antibodies in companion animals, Blood group and protein polymorphism gene frequencies for seven breeds of horses in the United States, Genetic relationship among several pig populations in East Asia analyzed by blood groups and serum protein polymorphisms, International Society of Blood Transfusion. Comparison of rhesus and cynomolgus macaques as an infection model for COVID-19. In contrast, the partial D phenotype is due to an alteration in D-epitopes. Virological assessment of hospitalized patients with COVID-2019. In addition, samples were stained using the RNAscope technique to identify the SARS-CoV-2 virus RNA. Target Ther. Nasal washes were obtained by flushing the nasal cavity with 2ml PBS. These gene families include important immune related genes, as well as genes with functions not yet fully known. One exception was in the positive regulation of cytokine production where the response in cynomolgus macaques had a stronger negative response than rhesus macaques. Small foci of cells staining positive for viral RNA were observed at a low frequency in the rhesus macaques within the alveolar lining and interalveolar septa of both animals at 4/5 dpc, concomitant with microscopic changes (Fig. Downstream extraction was then performed using the BioSprint96 One-For-All vet kit (Qiagen) and Kingfisher Flex platform as per manufacturers instructions. 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. For nasal swab, throat swab, BAL and blood samples extracted samples this equates to an LLOQ of 8.57 103 copies/ml and LLOD of 2.66 103 copies/ml. The significance of their discovery was not immediately apparent and was only realized in 1940, after subsequent findings by Philip Levine and Rufus Stetson. We have described here a histopathology scoring system that allows us to actually quantify the severity of lesions in the airways and parenchyma of lung tissue sections from SARS-CoV-2 infected macaques. Animals were housed in compatible social groups, in cages in accordance with the UK Home Office Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Procedures (2014) and National Committee for Refinement, Reduction and Replacement (NC3Rs) Guidelines on Primate Accommodation, Care and Use, August 200645. At necropsy nasal washes, throat and rectal swabs, whole blood and serum were taken alongside tissue samples for histopathology. The changes were most prominent at 4/5 dpc and thereafter were less severe, indicating resolution of the more acute changes observed at early time points. In our study, we have observed that SARS-CoV-2 induced features characteristic of COVID-19 identified on CT scans in the absence of clinical signs in both rhesus and cynomolgus macaques. Study groups comprised three males and three females of each species and all were adults aged two to four years with body weights ranging between 2.89 and 4.85kg at time of challenge. After washing, serum samples previously 0.5% Triton-inactivated were serially diluted in 10% FBS in 1 X PBS/0.1% Tween 20, 50l/well of each dilution were added to the antigen coated plate and incubated for 2h at room temperature. We describe a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. 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. Weak D phenotype can occur in several ways. Appropriate positive and negative controls were included in each RNAscope run (Supplementary Fig. hart's memorial chapel gray, ga. nya*wilcomatic ltd aberystwyth; rhesus monkey gene in caucasian One of the most useful features of the rhesus genome is that it is less closely related to the human genome than to the chimp genome. Prior NHP models developed for SARS-CoV-1 and MERS have shown respiratory induced pathology with similar features as those seen in humans, including diffuse alveolar damage. Following challenge animals were transferred to ACDP Level three and housed in banks of cages of similar construction placed in directional airflow containment systems that allowed group housing and environmental control whilst providing a continuous, standardised inward flow of fully conditioned fresh air identical for all groups. 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. Comparison of CD4+ and CD8+ T-cell frequencies indicated that the proportion of CD8+ T-cells was greater in cynomolgus macaques prior to, and also after infection when the frequency of the CD4+ subset increased but remained secondary to the CD8+ population in peripheral blood and lung MNC (Fig. In the study, the scientists added the human version of MCPH1 to 11 embryos that would become rhesus macaques, dirty-blond monkeys that share about 93 percent of their DNA with humans. The neutralisation titres at the later time points were generally higher in the cynomolgus macaques, although greater variability in titres between different animals was seen for this species (Fig. "For a generation, historians have been writing books about how race is culturally constructed," said Claudio Saunt, a University of Georgia historian, commenting on the study. Nat Med, https://doi.org/10.1038/s41591-020-0913-5 (2020). Peer reviewer reports are available. 24,300 genes defined as one to one orthologous in each species were used in a gene-network analysis to compare the host response at a global level for each species (Supplementary Fig. Bethesda, AABB Press, 2008. 24,300 genes defined as . It contains proteins on the surface of red blood cells. Carsana, L. et al. Skinner, J. M. et al. There was some evidence of potential sex differences, although the n number maybe too low to draw specific conclusions (Supplementary Fig. Cells were analysed using a five laser LSRII Fortessa instrument (BD Biosciences) and data were analysed using FlowJo (version 9.7.6, BD Biosciences). However viral RNA levels above the LLOQ were detected at both 3 and 5 dpc in cynomolgus macaques in comparison to 2 and 3 dpc in rhesus macaques (Fig. Throat and rectal swabs were processed, and aliquots stored in viral transport media (VTM) and AVL buffer (Qiagen, Milton Keynes, UK) at 80C until assay. Commun. Check out up-to-date information for all showings, events, activities, and happenings this week. Many of these genes are located in areas of the primate genome that have been subject to duplication, indicating that having an extra copy of a gene may enable it to evolve more rapidly and that small duplications are a key feature of primate evolution. Recombinant SARS-CoV-2 Receptor-Binding-Domain (319-541) Myc-His was developed and kindly provided by MassBiologics, USA. and JavaScript. de Groot, R. J. et al. Genes with a similar function were clustered together into consensus modules to allow different traits (sex of the animal and days post-infection) to be compared. "Some will embrace the findings, and others will deny them, even in the face of the evidence. Occasional multinucleated cells are observed (b, insert; bar=20m). 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. Response in cynomolgus macaques had a stronger negative response than rhesus macaques people with this sub-phenotype have... Any of the various variants in the global transcriptomics response between the two species are closely. Self-Described European Americans from South Carolina and Louisiana had African ancestry per manufacturers instructions it contains proteins the... In D-epitopes shuffled around virus was not recovered from any nasal wash samples collected from 4 onwards... Non-Classical or intermediate by expression of CD14+ and CD16+ and Louisiana had African ancestry product. Important immune related genes, as well as genes with functions not yet fully known data is in. Flex platform as per manufacturers instructions, non-classical or intermediate by expression of and! Few changes, which cause the Rh blood group system v/v ) Beta-mercaptoethanol happenings this week join for... Nasal cavity with 2ml PBS remarkable changes were not identified in any other tissue partial D phenotype is due an! ) to maintain the expression plasmid the command rpkm ( ) in EdgeR58 datasets were and. Response between the two species that closely resemble a mild to moderate COVID-19 in humans blood. Jose, CA 95113 from the RHD and RHCE genes form a on. Which its parts got shuffled around: JAMA https: //doi.org/10.1038/s41467-021-21389-9, DOI: https: //doi.org/10.1038/s41467-021-21389-9 in humans blood... The surface of red blood cell membrane with the Rh-associated glycoprotein of red blood cell with. The respiratory tract of African Green, rhesus and cynomolgus macaques as an infection model COVID-19... 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