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Innate and adaptive immune responses to SARS-CoV-2 in Syrian hamsters disclosed by single-cell sequencing and high-throughput proteomics

ABSTRACT: We describe the cellular response to SARS-CoV-2 infections in lung and blood of Syrian gold hamsters Single-cell RNA-sequencing and proteomics was performed from lung and blood of infected animals at different time points post infection

ORGANISM(S): Mesocricetus auratus

PROVIDER: GSE162208 | GEO | 2020/12/15

REPOSITORIES: GEO

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Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

Project description:We tested if Brd2 inhibitor ABBV-744 could reduce SARS-CoV-2 infection in Syrian Hamsters. Three days post-infection, the lungs of hamsters were harvested and subjected to RNA-seq. Infected, but untreated, hamsters showed marked up-regulation of a number of genes including ISGs when compared to uninfected controls. In contrast, hamsters treated with ABBV-744 showed a down-regulation of ISG levels, confirming ABBV-744 activity. Thus, Brd2 inhibition can decrease SARS-CoV-2 infection in Syrian Hamsters.

2021-09-02 | GSE182994 | GEO

Bulk RNA sequencing in SARS-CoV-2-infected hamsters

Project description:We report the application of bulk RNA sequencing technology for high-throughput profiling of SARS-CoV-2 infection in the lung of Syrian golden hamsters (Mesocricetus auratus).

2022-05-26 | GSE204696 | GEO

Changes in the gene expression in the inferior colliculus of the sound stimulated both control Syrian hamsters and the strain GASH:Sal.

Project description:Using microarray analyses and subsequent verification by RT-PCR, we studied the changes in gene expression in the inferior colliculus after an ictal event in one models of audiogenic epilepsy, genetic audiogenic seizure hamster (GASH:Sal). GASH:Sal, a hamster strain developed at the University of Salamanca, exhibits genetic audiogenic epilepsy similar to human Grand Mal epilepsy. GASH:Sal shows an autosomal recessive inheritance for susceptibility to audiogenic seizures, which manifest more severely in young animals; the seizure severity progressively declines with age. Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were subjected to auditory stimulation, and 60 minutes after stimulation, the inferior colliculi were collected. As a control, intact Wistar rats and Syrian hamsters were subjected to identical stimulation and tissue preparation protocols to those performed on the experimental animals. A total of 24 animals were used in this study according to the following distribution: 12 control Syrian hamsters (Mesocricetus auratus) and 12 GASH:Sal at 16 weeks of age and a body weight of approximately 60 g. Six animals Syrian and GASH:Sal hamsters, respectively, were exposed to auditory stimulation, and 60 min after the seizures, we harvested the IC for all gene expression analyses (stimulated Syrian hamsters and stimulated GASH:Sal hamsters). As controls, other six animals Syrian and GASH:Sal hamsters, respectively, were not exposed to the same stimulation (Syrian hamsters and GASH:Sal hamsters).

2015-12-31 | E-GEOD-74043 | biostudies-arrayexpress

A Single Intranasal Vaccination with a Rationally Attenuated SARS-CoV-2 Elicits Strong Humoral Immune Response and Is Protective in Syrian Hamsters

Project description:Very few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are currently in pre-clinical or clinical development. We rationally attenuated SARS-CoV-2 (isolate WA1/2020) by removing the polybasic cleavage site within the spike protein and the open reading frames (ORFs) 6-8, and by introducing a pair of mutations into the non-structural protein 1 (Nsp1). The derived virus (WA1-DPRRA-ORF6-8-Nsp1K164A/H165A) became severely attenuated in both the K18-human ACE2 (hACE2) transgenic mice and in Syrian hamsters. Transcriptomic profiling of nasal turbinates and lung tissues of infected Syrian hamsters confirmed that WA1-DPRRA-ORF6-8-Nsp1K164A/H165A attenuated the upregulation of proinflammatory pathways. A single intranasal immunization of just 100 PFU of the WA1-DPRRA-ORF6-8-Nsp1K164A/H165A elicited binding and neutralizing antibody responses in Syrian hamsters and completely protected against SARS-CoV-2-induced weight loss and pneumonia. These data demonstrate the feasibility of rational attenuation of SARS-CoV-2. WA1-DPRRA-ORF6-8-Nsp1K164A/H165A represents a promising live attenuated vaccine candidate.

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Prior influenza infection mitigates SARS-CoV-2 disease in Syrian hamsters

Project description:Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1) interactions in Syrian hamsters. H1N1 given 48 hours prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by normalization of granulocyte dynamics and accelerated antigen presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 hour dual infected animals. Dual infected animals also experienced significant transient downregulation of mitochondrial and viral replication pathways. By quantitative RT-PCR, we confirmed reduced SARS-CoV-2 viral load and lower cytokine levels throughout disease course in lung of dual infected animals. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

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Duper is a Cryptochrome 1 null mutation in Syrian hamsters

Project description:The duper mutation is a recessive mutation that shortens the period length of the circadian rhythm in Syrian hamsters. These animals show a large phase shift when responding to light pulses. Using two distinct ecotypes and a fast homozygosity mapping strategy, we identified duper as an early nonsense allele of Cryptochrome 1 (Cry1) leading to a short, unstable protein.

2022-04-18 | GSE184205 | GEO

Mesocricetus auratus breed:Golden Syrian hamsters

Project description:Mesocricetus auratus breed:Golden Syrian hamsters Metagenomic assembly

| PRJNA326307 | ENA

Temporal and dosage-dependent transcriptional response to SARS-CoV-2 in lung, trachea, brain, olfactory bulb and small intestine of Syrian golden hamsters

Project description:Here we report the transcriptional response to SARS-CoV-2 in Syrian golden hamsters and compare it to the host response against Influenza A virus. The virus replicates fast to high titers in the respiratory tract followed by a local and systemic inflammatory response. A roust IFN-I reponse is mounted and lasts at leaset fourteen days in distal tissues together with other lasting transcriptional changes.

2020-11-11 | GSE161200 | GEO

Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

Project description:Brd2 inhibitor ABBV-744 inhibits SARS-CoV-2 infection in Syrian Hamsters

| PRJNA758692 | ENA

SARS-CoV-2 disease severity and transmission efficiency is increased for airborne compared to fomite exposure in Syrian hamsters.

Project description:Transmission of SARS-CoV-2 is driven by contact, fomite, and airborne transmission. The relative contribution of different transmission routes remains subject to debate. Here, we show Syrian hamsters are susceptible to SARS-CoV-2 infection through intranasal, aerosol and fomite exposure. Different routes of exposure present with distinct disease manifestations. Intranasal and aerosol inoculation causes severe respiratory pathology, higher virus loads and increased weight loss. In contrast, fomite exposure leads to milder disease manifestation characterized by an anti-inflammatory immune state and delayed shedding pattern. Whereas the overall magnitude of respiratory virus shedding is not linked to disease severity, the onset of shedding is. Early shedding is linked to an increase in disease severity. Airborne transmission is more efficient than fomite transmission and dependent on the direction of the airflow. Carefully characterized SARS-CoV-2 transmission models will be crucial to assess potential changes in transmission and pathogenic potential in the light of the ongoing SARS-CoV-2 evolution

2021-08-04 | GSE177027 | GEO

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