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Establishment of an African green monkey model for COVID-19 and protection against re-infection.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen vaccines and treatments. We show that African green monkeys (AGMs) support robust SARS-CoV-2 replication and develop pronounced respiratory disease, which may more accurately reflect human COVID-19 cases than other nonhuman primate species. SARS-CoV-2 was detected in mucosal samples, including rectal swabs, as late as 15 days after exposure. Marked inflammation and coagulopathy in blood and tissues were prominent features. Transcriptome analysis demonstrated stimulation of interferon and interleukin-6 pathways in bronchoalveolar lavage samples and repression of natural killer cell- and T cell-associated transcripts in peripheral blood. Despite a slight waning in antibody titers after primary challenge, enhanced antibody and cellular responses contributed to rapid clearance after re-challenge with an identical strain. These data support the utility of AGM for studying COVID-19 pathogenesis and testing medical countermeasures.

SUBMITTER: Woolsey C

PROVIDER: S-EPMC7790436 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Establishment of an African green monkey model for COVID-19.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been employed in other NHP studies.

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Transcriptomic resource of African green monkey (Chlorocebus aethiops sabaues)

Project description:Characterization of transcriptomic variation is emerging as a critical tool for understanding how quantitative trait loci (QTL) contribute to complex phenotypes. Human transcriptomic studies are limited by factors such as the feasibility of invasive tissue collection or variable environmental exposures that can be readily overcome in non-human primate (NHP) models. We characterized transcriptomic variation across multiple tissues and developmental stages and between individuals in 59 vervet monkeys from the Vervet Research Colony extended pedigree. We conducted RNA sequencing across early (7, 90 days, and one year) and later (1.25, 1.5, 1.75, 2, 2.5, 3, and 4+ years old) developmental time points in 6 individuals at each stage in five tissue types: two brain tissues from hippocampus and caudate, two endocrine tissues (pituitary and adrenal) and two peripheral tissues serving as a source of biomarkers (blood and fibroblasts)

2014-02-12 | E-MTAB-4404 | biostudies-arrayexpress

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Insights into the dual activity of SIVmac239 Vif against human and African green monkey APOBEC3G.

Project description:Human immunodeficiency virus type 1 (HIV-1) Vif is essential for viral evasion of the host antiviral protein APOBEC3G (APO3G). The Vif protein from a distantly related African green monkey (Agm) simian immunodeficiency virus (SIVagm) is unable to suppress the antiviral activity of human APO3G but is active against Agm APO3G. SIVmac Vif on the other hand, possesses antiviral activity against both human and Agm APO3G. In this study, we were interested in mapping domains in SIVmac Vif that are responsible for its dual activity against human and Agm APO3G. We constructed a series of Vif chimeras by swapping domains in SIVmac Vif with equivalent regions from SIVagm Vif and determined their activity against human and Agm APO3G. We found that replacing any region in SIVmac Vif by corresponding fragments from SIVagm Vif only moderately reduced the activity of the chimeras against Agm APO3G but in all cases resulted in a severe loss of activity against human APO3G. These results suggest that the domains in SIVmac Vif required for targeting human and Agm APO3G are distinct and cannot be defined as linear amino acid motifs but rather appear to depend on the overall structure of full-length SIVmac Vif.

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Project description:The four serotypes of mosquito-borne dengue virus (DENV-1, -2, -3, and -4) that circulate in humans each emerged from an enzootic, sylvatic cycle in non-human primates. Herein, we present the first study of sylvatic DENV infection dynamics in a primate. Three African green monkeys were inoculated with 10(5) plaque-forming units (pfu) DENV-2 strain PM33974 from the sylvatic cycle, and one African green monkey was inoculated with 10(5) pfu DENV-2 strain New Guinea C from the human cycle. All four monkeys seroconverted (more than fourfold rise in 80% plaque reduction neutralization titer [PRNT80]) against the strain of DENV with which they were inoculated; only one (33%) of three monkeys infected with sylvatic DENV showed a neutralizing antibody response against human-endemic DENV. Virus was detected in two of three monkeys inoculated with sylvatic DENV at low titer (≤ 1.3 log10pfu/mL) and brief duration (≤ 2 days). Clinical signs included rash and elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.

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Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

Project description:BACKGROUND:Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS:We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE:Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.

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Human polyomavirus related to African green monkey lymphotropic polyomavirus.

Project description:While studying the virome of the skin surface of a patient with a Merkel cell carcinoma (MCC) by using unbiased, high-throughput sequencing, we identified a human polyomavirus nearly identical to human polyomavirus 9, a virus recently reported in blood and urine of renal transplantion patients and closely related to the African green monkey lymphotropic polyomavirus. Specific PCR analysis further identified this virus in 2/8 patients with MCC but in only 1/111 controls without MCC. This virus was shed for ≥20 months by the MCC index patient and was on the skin of the spouse of the index patient. These results provide information on the viral ecology of human skin and raise new questions regarding the pathology of virus-associated skin disorders.

| S-EPMC3381546 | biostudies-literature

Long Oligonucleotide Microarrays for African Green Monkey Gene Expression Profile Analysis

Project description:Nonhuman primates including African Green Monkey (AGM) are important models for biomedical research. The information on monkey genomes is still limited and no versatile gene expression screening tool is available. We tested human whole genome microarrays for cross-species reactivity with AGM transcripts using both long oligonucleotide arrays (60-mer probes, Applied Biosystems-ABI) and short oligonucleotide arrays (25-mer, Affymetrix). Using the long oligonucleotide arrays we detected four times more AGM transcripts than with the short oligonucleotide technology. The number of detected transcripts was comparable to that detected using human RNA, with 87% of the detected genes being shared between both species. The specificity of the signals obtained with the long oligonucleotide arrays was determined by analyzing the transcriptome of concanavalin A activated CD4+ T cells versus non-activated T cells of two monkey species AGM and macaque. For both species, the genes showing the most significant changes in expression, such as IL-2R, were those known to be also regulated in human CD4+ T cell activation. Finally, tissue-specificity of the signals was established by comparing the transcription profiles of AGM brain and tonsil cells. In conclusion, the ABI human microarray platform provides a highly valuable tool for the assessment of AGM gene expression profiles. Keywords: Defining a microarray platform to study the AGM transcriptome by cross-species and cross-platform comparison

2007-10-01 | GSE6982 | GEO

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