Transcriptional comparison of cynomolgus macaques (Macaca fascicularis) following infection with Lassa or Lujo viruses
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ABSTRACT:
ORGANISM(S): Macaca fascicularis Macaca mulatta
PROVIDER: GSE49838 | GEO | 2014/08/29
SECONDARY ACCESSION(S): PRJNA215072
REPOSITORIES: GEO
Similar Datasets
Project description:Microarray analysis of PBMC from cynomolgus macaques collected longitudinally over the course of infection with Lassa-Josiah, Lassa-Z132, Lassa-SorombaR, or Lujo viruses (n=3 animals/infection condition). 3 macaques from each group were infected intramuscularly with 10^4 PFU of Lassa-Josiah, Lassa-Z132, Lassa-SorombaR, or Lujo viruses. PBMC were collected at days 1, 4, 7, 10, 13, and 29 (for surviving animals). We performed microarray analysis on PBMC samples using Agilent rhesus macaque arrays on all samples, as well as on PBMC from 3 uninfected animals for use as a control.
2014-08-29 | E-GEOD-49838 | biostudies-arrayexpress
Project description:Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
2023-02-21 | GSE225258 | GEO
Project description:Background: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration. Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. In a second approach, ERV-K-(HML-2) RNA and protein expression was analysed in extracts from the same cynomolgus macaques.
2011-06-10 | E-GEOD-29818 | biostudies-arrayexpress
Project description:Transcriptional comparison of cynomolgus macaques (Macaca fascicularis) following infection with Lassa or Lujo viruses
| PRJNA215072 | ENA
Project description:Cynomolgus macaques (Macaca fascicularis) are used widely in biomedical research, and the genetics of their MHC (Mhc-Mafa) has become the focus of considerable attention in recent years. The cohort of Indonesian pedigreed macaques that we present here was typed for Mafa-A, -B, and -DR, by sequencing, as described in earlier studies. Additionally, the DRB region of these animals was characterised by microsatellite analyses. In this study, full-length sequencing of Mafa-DPA/B and -DQA/B in these animals was performed. A total of 75 different alleles were observed; 22 of which have not previously been reported, plus 18 extended exon 2 alleles that were already known. Furthermore, two microsatellites, D6S2854 and D6S2859, were used to characterise the complex Mafa-A region. Sequencing and segregation analyses revealed that the length patterns of these microsatellites are unique for each Mafa-A haplotype. In this work, we present a pedigreed colony of approximately 120 cynomolgus macaques; all of which are typed for the most significant polymorphic MHC class I and class II markers. Offspring of these pedigreed animals are easily characterised for their MHC by microsatellite analyses on the Mafa-A and -DRB regions, which makes the cumbersome sequencing analyses redundant.
| S-EPMC3438390 | biostudies-literature
Project description:Background: Prion diseases such as bovine spongiform encephalopathies (BSE) are transmissible neurodegenerative diseases which are presumably caused by an infectious conformational isoform of the cellular prion protein. Previous work has provided evidence that in murine prion disease the endogenous retrovirus (ERV) expression is altered in the brain. To determine if prion-induced changes in ERV expression are a general phenomenon we used a non-human primate model for prion disease. Results: Cynomolgus macaques (Macaca fasicularis) were infected intracerebrally with BSE-positive brain stem material from cattle and allowed to develop prion disease. Brain tissue from the basis pontis and vermis cerebelli of the six animals and the same regions from four healthy controls were subjected to ERV expression profiling using a retrovirus-specific microarray and quantitative real-time PCR. We could show that Class I gammaretroviruses HERV-E4-1, ERV-9, and MacERV-4 increase expression in BSE-infected macaques. In a second approach, we analysed ERV-K-(HML-2) RNA and protein expression in extracts from the same cynomolgus macaques. Here we found a significant downregulation of both, the macaque ERV-K-(HML-2) Gag protein and RNA in the frontal/parietal cortex of BSE-infected macaques. Conclusions: We provide evidence that dysregulation of ERVs in response to BSE-infection can be detected on both, the RNA and the protein level. To our knowledge, this is the first report on the differential expression of ERV-derived structural proteins in prion disorders. Our findings suggest that endogenous retroviruses may induce or exacerbate the pathological consequences of prion-associated neurodegeneration.
2011-06-10 | GSE29818 | GEO
Project description:BackgroundNonhuman primates are commonly used in biomedical research as animal models of human disease and behavior. Compared to common rodent models, nonhuman primates are genetically, physiologically, behaviorally and neurologically more similar to humans owing to more recent shared ancestry and therefore provide the advantage of greater translational validity in preclinical studies. The cynomolgus macaque (Macaca fascicularis) is one of the most commonly used nonhuman primates in academic and industry settings, yet population genetic research has revealed significant substructure throughout the species distribution that may confound studies. Cynomolgus monkeys introduced to Mauritius specifically have previously been thought to maintain the least genetic heterogeneity of all cynomolgus monkeys, although recent work, including work from our lab, suggests macaques from Mauritius too may harbor cryptic substructure.ResultsTo evaluate putative substructure in Mauritian cynomolgus macaques, we designed a panel of 96 single nucleotide polymorphisms based on preliminary findings from previous work to screen 246 of cynomolgus monkeys from two primary suppliers. Results from this study support substructure in Mauritian macaques and suggest a minimum of two populations and maybe three on Mauritius, with moderate admixture.ConclusionThese findings inform the natural history of these monkeys suggesting either a previously unrecognized physical or ecological barrier to gene flow on Mauritius and/or the breakdown of historic substructure resulting from the history of macaque introduction to the island. These findings are relevant to ongoing research using these models in part because of increased appreciation of segregating common variation with functional effects and may be used to better inform animal selection in preclinical research.
| S-EPMC4167525 | biostudies-literature
Project description:BackgroundMacaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. Little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, Macaca mulatta (rhesus macaque). Previously we identified single nucleotide polymorphisms (SNPs) in portions of 94 rhesus macaque genes and reported that Indian and Chinese rhesus had largely different SNPs. Here we identify SNPs from some of the same genomic regions of cynomolgus macaques (from Indochina, Indonesia, Mauritius and the Philippines) and compare them to the SNPs found in rhesus.ResultsWe sequenced a portion of 10 genes in 20 cynomolgus macaques. We identified 69 SNPs in these regions, compared with 71 SNPs found in the same genomic regions of 20 Indian and Chinese rhesus macaques. Thirty six (52%) of the M. fascicularis SNPs were overlapping in both species. The majority (70%) of the SNPs found in both Chinese and Indian rhesus macaque populations were also present in M. fascicularis. Of the SNPs previously found in a single rhesus population, 38% (Indian) and 44% (Chinese) were also identified in cynomolgus macaques. In an alternative approach, we genotyped 100 cynomolgus DNAs using a rhesus macaque SNP array representing 53 genes and found that 51% (29/57) of the rhesus SNPs were present in M. fascicularis. Comparisons of SNP profiles from cynomolgus macaques imported from breeding centers in China (where M. fascicularis are not native) showed they were similar to those from Indochina.ConclusionThis study demonstrates a surprisingly high conservation of SNPs between M. fascicularis and M. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial DNA analysis alone. These findings indicate that SNP discovery efforts in either species will generate useful resources for both macaque species. Identification of SNPs that are unique to regional populations of cynomolgus macaques indicates that location-specific SNPs could be used to distinguish monkeys of uncertain origin. As an example, cynomolgus macaques obtained from 2 different breeding centers in China were shown to have Indochinese ancestry.
| S-EPMC2248198 | biostudies-literature
Project description:Cynomolgus macaques are common across South East Asian countries including Thailand. The National Primate Research Center of Thailand, Chulalongkorn University (NPRCT-CU) captures wild-borne cynomolgus macaque for research use. Limited information is available on the enteric viruses and possible zoonotic infections into or from cynomolgus macaques. We characterized and compare the fecal virome of two populations; healthy wild-originated captive cynomolgus macaques (n = 43) reared in NPRCT-CU and healthy wild cynomolgus macaques (n = 35). Over 90% of recognized viral sequence reads amplified from feces were from bacterial viruses. Viruses from seven families of mammalian viruses were also detected (Parvoviridae, Anelloviridae, Picornaviridae, Adenoviridae, Papillomaviridae, Herpesviridae, and Caliciviridae). The genomes of a member of a new picornavirus genus we named Mafapivirus, a primate chapparvovirus, and a circular Rep-encoding single-strand (CRESS) DNA virus were also characterized. Higher abundance of CRESS DNA viruses of unknown tropism and invertebrate-tropic ambidensovirus were detected in wild versus captive macaques likely reflecting dietary differences. Short term rearing in captivity did not have a pronounced effect on the diversity of mammalian viruses of wild cynomolgus macaques. This study is the first report of the fecal virome of cynomolgus macaques, non-human primates frequently used in biomedical research and vaccination studies.
| S-EPMC6832579 | biostudies-literature
Project description:Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We compared the efficacy of measles-based and Mopeia-based vaccine platforms against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from Lassa virus infection and disease after a single immunization but with different efficacy. Analyses of immune responses demonstrated that complete protection was associated with early and robust T-cell responses against LASV but not humoral responses nor neutralizing antibodies. Transcriptomic and proteomic analyses performed during the immunization phase confirmed the role of early innate immunity and T-cell priming in vaccine efficacy and showed specific profiles detectable as early as two days after immunization. The most efficient candidate, measles vector expressing simultaneously LASV glycoprotein and nucleoprotein, will be soon evaluated in phase I clinical trial.
2019-06-20 | GSE132998 | GEO