Related Experiment Video
Updated: Mar 24, 2026
Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
Neurotropism of Saffold virus in a mouse model
Frédéric Sorgeloos1, Cécile Lardinois2, Sophie Jacobs2
1Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, UK.
Abstract:
Saffold virus (SAFV) is a highly seroprevalent human Cardiovirus discovered recently. No clear association between SAFV infection and human disease has been established. Rare infection cases, however, correlated with neurological symptoms. To gain insight into the pathogenesis potential of the virus, we performed experimental mouse infection with SAFV strains of genotypes 2 and 3 (SAFV-2 and SAFV-3). After intraperitoneal infection, both strains exhibited a typical Cardiovirus tropism. Viral load was most prominent in the pancreas. Heart, spleen, brain and spinal cord were also infected. In IFN-receptor 1 deficient (IFNAR-KO) mice, SAFV-3 caused a severe encephalitis. The virus was detected by immunohistochemistry in many parts of the brain and spinal cord, both in neurons and astrocytes, but astrocyte infection was more extensive. In vitro, SAFV-3 also infected astrocytes better than neurons in mixed primary cultures. Astrocytes were, however, very efficiently protected by IFN-α/β treatment.
Insights
Saffold virus (SAFV) infection can cause severe neurological symptoms in mice lacking a functional interferon receptor. Astrocytes are particularly vulnerable to SAFV-3, but can be protected by interferon therapy.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Saffold virus (SAFV) is a recently identified human Cardiovirus with high seroprevalence.
- While generally asymptomatic, rare SAFV infections have been linked to neurological disorders.
- The pathogenic potential of SAFV remains largely unknown.
Purpose of the Study:
- To investigate the pathogenesis of Saffold virus (SAFV) genotypes 2 and 3 (SAFV-2 and SAFV-3) in a mouse model.
- To determine the tropism and disease potential of SAFV infection, particularly in the context of interferon signaling.
- To explore the susceptibility of neural cells to SAFV infection and the efficacy of interferon treatment.
Main Methods:
- Experimental infection of mice with SAFV-2 and SAFV-3 via intraperitoneal injection.
- Analysis of viral load and tissue tropism, including the pancreas, heart, spleen, brain, and spinal cord.
- Infection of interferon-receptor 1 deficient (IFNAR-KO) mice to assess encephalitis development.
- In vitro studies using mixed primary cultures of neurons and astrocytes to evaluate cellular tropism and response to interferon-alpha/beta (IFN-α/β) treatment.
Main Results:
- Both SAFV-2 and SAFV-3 demonstrated typical Cardiovirus tropism, with the highest viral loads observed in the pancreas.
- SAFV-3 infection in IFNAR-KO mice led to severe encephalitis, with the virus detected in both neurons and astrocytes within the brain and spinal cord.
- Astrocyte infection was more extensive than neuronal infection in vivo and in vitro.
- In vitro, astrocytes were effectively protected from SAFV-3 by IFN-α/β treatment.
Conclusions:
- SAFV can infect various organs, including the central nervous system.
- Impaired interferon signaling, as seen in IFNAR-KO mice, exacerbates SAFV pathogenesis, leading to encephalitis.
- Astrocytes are a primary target for SAFV-3 in the central nervous system, but they retain sensitivity to interferon-mediated protection.
