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. 382, 17081720 (2020). The slightly increased levels of clinical changes previously described in rhesus12,24,25 may be due to the use of the ocular and oral routes in addition to IN and IT for challenge and the potential impact of additional in-life sampling. 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. CAS After the ABO blood group system, it is the most likely to be involved in transfusion . https://doi.org/10.5694/mja2.50569 (2020). A novel acute respiratory syndrome, now called Coronavirus disease-19 (COVID-19) was first reported in China in December 2019. 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. This is considered to represent a mild, frequently observed background lesion. 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Further information on research design is available in theNature Research Reporting Summary linked to this article. As humans and chimps gradually evolved from a common ancestor, their DNA, passed from generation to generation, changed too. Gene expression analysis by defining mRNA profiles in clinical samples can be used to characterise the host response to infection. Caly, L. et al. Falsey, A. R. & Walsh, E. E. Novel coronavirus and severe acute respiratory syndrome. [45] Only 43 individuals have been reported to have it worldwide. Since Amt is found in really ancient lifeforms like Archaea, we know that Rh must have evolved from that more ancient protein. 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. 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. Bioinformatics 26, 139140 (2010). 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. CAS Digital image analysis was performed in RNAscope labelled slides to ascertain the percentage of stained cells within the lesions, by using the Nikon-NIS-Ar package. Sections were analysed by two qualified veterinary pathologists and peer-reviewed by two other qualified pathologists (veterinary and medical). 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. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in performed animal procedures and sampling processing. IgG seroconversion occurred in both macaque species from days 8-9 post-infection and therefore follows a similar kinetic to serology profiles measured in COVID-19 patients33, indicating that both species offer representative models for the investigation of SARS-CoV-2 related humoral immunity. Post-mortem examination and sample collection were performed immediately after confirmation of death. 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. Can Rh factor be found in other animals? 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. 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. The frequency of Th17 and TNF- expressing cells differed between the species with IL-17 producing CD4 and CD8 T-cells more prevalent in rhesus macaques, whereas TNF expression was detected more frequently in cynomolgus macaques. Cells 1, 514 (2012). [citation needed], The D antigen is inherited as one gene (RHD) (on the short arm of the first chromosome, p36.13p34.3) with various alleles. Clin. Viral load presented as the geometric mean of RNA copies/mL or individual values, with individual data points overlaid in rhesus macaques (blue) and cynomolgus macaques (red) in (a) nasal wash total RNA, (b) nasal wash Sg RNA, (c) throat swab total RNA, (d) throat swab Sg RNA (e) bronchoalveolar lavage (BAL) total RNA, (f) bronchoalveolar lavage (BAL) Sg RNA (numbers indicate days post-challenge the NHP was euthanised), (g) rectal swab total RNA, (h) whole blood total RNA. It was discovered in 1937 by Karl Landsteiner and Alexander S. Wiener, who, at the time, believed it to be a similar antigen found in rhesus macaque red blood cells. If both of a child's parents are Rh negative, the child will definitely be Rh negative. 23andMe was the first source that could offer this kind of data.". An inheritable form also occurs, as a result of a weakened form of the R0 gene. Nature 579, 482483 (2020). Zhang, S. America is running low on a crucial resource for COVID-19 vaccines. A single dose of ChAdOx1 MERS provides protective immunity in rhesus macaques. Wolfel, R. et al. In Africans, there are three molecular backgrounds that give rise to the Rh D-phenotype which is found in 8% of the population. Oklahoma, the study revealed, has the highest proportion of self-identified African-Americans with Native American genes. Nasal washes were obtained by flushing the nasal cavity with 2ml PBS. Virus was not recovered from any nasal wash samples collected from 4 dpc onwards. After 48 hours of birth, the newborn may be allowed to nurse from its mother as her antibodies can no longer be absorbed through the neonates intestines. Immunol. devised the scan protocols, the scoring system and reported the CT scans. Target Ther. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Learn more about the iconic tradition of inspiring young innovators. Bars in micrographs=200m. Cells were stimulated overnight with SARS-CoV-2 peptide pools and megapools of the spike protein (Mimotopes, Australia). To obtain Severity ranges from 0 to 4: 0=none; 1=minimal; 2=mild; 3=moderate and 4=marked/severe. Behaviour was evaluated for contra-indicators including depression, withdrawal from the group, aggression, changes in feeding patterns, breathing pattern, respiration rate and cough. Rhesus macaques summed MP nave vs late time point p=0.01. 102, Unit 12 14, https://doi.org/10.1002/0471142735.im1214s102 (2013). [3], Notations of the two theories are used interchangeably in blood banking (e.g., Rho(D) meaning RhD positive). [52] In May 1941, the third anti-Rh serum (M.S.) Grifoni, A. et al. 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. When they did this comparison, scientists also found that Rh is very similar to a different molecule: Amt. However, there are exceptions: for instance, Japanese and black Africans may have an intact gene that is not expressed or only at very low levels. Based on different models of genetic inheritance, two different terminologies were developed; both of them are still in use. These Rh molecules from different animals have the same biochemical function-differing slightly in their amino acid sequences. medRxiv https://doi.org/10.1101/2020.04.14.20065771 (2020). Transl. https://doi.org/10.1016/S1473-3099(20)30434-5 (2020). et al. Image analysis of positively stained area in RNASCope labelled sections for IL-6 mRNA (j, areas of lesion); n=2 macaques per species and time point; bars represent median values. 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. Even a few kinds of bacteria have Rh molecules. Marcel, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. The BCM-HGSC has sequenced the genome of the rhesus monkey (rhesus macaque, Macaca mulatta). J. Virol. The overall change in reaction times was always larger in the RhD-negative group than in the RhD-positive. 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). Visit our corporate site (opens in new tab). "This article uses another tool, DNA analysis, to get at the same question.". What differs between Rh disease and NI is the pathogenesis of hemolysis between human fetuses and the animal species. 3). This revealed an increased frequency of transitional CD14+ CD16+ and non-classical CD14 CD16+ monocyte subsets in PBMCs collected at the later post-infection time point in both rhesus and cynomolgus species. Weighed tissue samples were homogenised and inactivated in RLT (Qiagen) supplemented with 1%(v/v) Beta-mercaptoethanol. Monocyte subtypes were characterised as classical, non-classical or intermediate by expression of CD14+ and CD16+. Get what matters in translational research, free to your inbox weekly. Only nine active donors have been reported. This system was based on the theory that a separate gene controls the product of each corresponding antigen (e.g., a "D gene" produces D antigen, and so on). Join us for Silicon Valley's most inspiring weekend! At necropsy nasal washes, throat and rectal swabs, whole blood and serum were taken alongside tissue samples for histopathology. At 14/15 and 18/19 dpc, only small areas of consolidation were observed. 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. The rhesus genomic DNA samples used for these studies were contributed by the California NPRC, Oregon NPRC, Southwest NPRC and Yerkes NPRC. F.V.G. Individuals with one or two copies of the short allele of the 5-HTT . 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. In the same way that DNA has instructions for what you might look like, it also has instructions for how your molecules get made. An international consortium of researchers has published the genome sequence of the rhesus macaque monkey and aligned it with the chimpanzee and human genomes. Weight and body temperature were monitored daily (Fig. https://doi.org/10.1038/s41591-020-0995-0 (2020). A serological assay to detect SARS-CoV-2 seroconversion in humans. Amplification of the signal was carried out following the RNAscope protocol using the RNAscope 2.5 HD Detection kitRed (Advanced Cell Diagnostics, Biotechne). anti-CD14-APC, anti-CD16-BV786, anti-CD20-PE-Dazzle (all from BioLegend); anti-CD3-AF700, anti-CD56-BV605, anti-HLA-DR-BUV395 (all from BD Biosciences); anti-CD159a-PC7 (Beckman Coulter) prepared in brilliant stain buffer. 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. conceived the study. In immunophenotyping datasets, classical-, non-classical-monocytes and monocyte derived dendritic cells (mDCs) were identified by FSC and SSC characteristics and by the expression pattern of HLA-DR, CD14, CD16 and CD11c within the live CD3-, CD20- population. PBMCs and MNC isolated from tissues were stored at 180C until resuscitated for analysis. Similar to Rockx et al.13 and Munster et al.12 we detected live virus, albeit at low levels in samples from the URT. Rev. Typically, Rhesus positive people have an intact RHD gene while negative people lack the gene (or have mutations in it). 4e). ADS 7, 5 (2020). & He, Q.-Y. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. What is Rhesus factor? Viral load in BAL samples echoed URT samples, with high (9.8 106 copies/ml) levels in both species at 4 and 5 dpc, dropping to 2.4 104 copies/ml and 1.9 104 copies/ml at 14 dpc and 15 dpc in rhesus and cynomolgus macaques, respectively (Fig. Group system, it is the pathogenesis of hemolysis between human fetuses and the animal species, rhesus people. Involved in transfusion slightly in their amino acid sequences to detect SARS-CoV-2 seroconversion in humans low on a crucial for... And body temperature were monitored daily ( Fig in new tab ) COVID-19! Macaque, Macaca mulatta ) collected from 4 dpc onwards, we know that Rh must have from! ( M.S. at low levels in samples from the URT the short allele of the spike protein (,! Qualified pathologists ( veterinary and medical ) article uses another tool, DNA analysis, to get at the biochemical... 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