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SJL/J mice are highly susceptible to infection by mouse adenovirus type 1
K R Spindler1, L Fang, M L Moore
1Department of Genetics, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia 30602, USA. spindler@arches.uga.edu
Abstract:
Mouse adenovirus type 1 (MAV-1) targets endothelial and monocyte/macrophage cells throughout the mouse. Depending on the strain of mouse and dose or strain of virus, infected mice may survive, become persistently infected, or die. We surveyed inbred mouse strains and found that for the majority tested the 50% lethal doses (LD(50)s) were >10(4.4) PFU. However, SJL/J mice were highly susceptible to MAV-1, with a mean LD(50) of 10(-0.32) PFU. Infected C3H/HeJ (resistant) and SJL/J (susceptible) mice showed only modest differences in histopathology. Susceptible mice had significantly higher viral loads in the brain and spleen at 8 days postinfection than resistant mice. Infection of primary macrophages or mouse embryo fibroblasts from SJL/J and C3H/HeJ mice gave equivalent yields of virus, suggesting that a receptor difference between strains is not responsible for the susceptibility difference. When C3H/HeJ mice were subjected to sublethal doses of gamma irradiation, they became susceptible to MAV-1, with an LD(50) like that of SJL/J mice. Antiviral immunoglobulin G (IgG) levels were measured in susceptible and resistant mice infected by an early region 1A null mutant virus that is less virulent that wild-type virus. The antiviral IgG levels were high and similar in the two strains of mice. Taken together, these results suggest that immune response differences may in part account for differences in susceptibility to MAV-1 infection.
Insights
Mouse adenovirus type 1 (MAV-1) susceptibility varies significantly between mouse strains. Immune response differences, not viral receptors, appear to influence MAV-1 infection outcomes in mice.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Mouse adenovirus type 1 (MAV-1) infects endothelial and immune cells in mice.
- MAV-1 infection outcomes (survival, persistence, death) depend on mouse strain, virus dose, and strain.
- Previous studies have not fully elucidated the factors contributing to differential MAV-1 susceptibility.
Purpose of the Study:
- To investigate the genetic basis of differential susceptibility to Mouse Adenovirus Type 1 (MAV-1) in inbred mouse strains.
- To identify the mechanisms underlying the observed variations in MAV-1 infection severity and lethality.
Main Methods:
- Determined 50% lethal doses (LD50) of MAV-1 across various inbred mouse strains.
- Compared histopathology, viral loads in tissues (brain, spleen), and in vitro viral replication in macrophages and fibroblasts from susceptible (SJL/J) and resistant (C3H/HeJ) strains.
- Assessed MAV-1 susceptibility in gamma-irradiated C3H/HeJ mice and measured antiviral immunoglobulin G (IgG) levels.
Main Results:
- SJL/J mice exhibited high susceptibility to MAV-1 (mean LD50 = 10(-0.32) PFU), unlike most other strains tested (LD50 >10(4.4) PFU).
- Susceptible mice showed significantly higher viral loads in the brain and spleen, despite similar histopathology and in vitro viral replication.
- Gamma irradiation rendered resistant C3H/HeJ mice susceptible to MAV-1, and antiviral IgG levels were comparable between susceptible and resistant strains.
Conclusions:
- Differences in immune response, rather than viral receptor variations, likely contribute to the observed strain-specific susceptibility to MAV-1.
- MAV-1 infection outcomes are significantly influenced by host immune status and genetic background.
- Further research into immune mechanisms is warranted to understand MAV-1 pathogenesis.