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Susceptible adult murine model for Junin virus
O E Campetella1, N V Galassi, N Sanjuan
1Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Abstract:
The adult mouse model had been considered resistant to Junin virus (JV) infection. However, we found that C3H/HeJ murine strain proved highly susceptible up to 5 months of age to intracerebral inoculation with the prototype XJ JV strain, showing neurological signs and 80-90% mortality within 13 days. Neutralizing antibodies (Nt Ab) were absent, but low immunofluorescent Ab levels (1:5) were detected as from day +7. The virus could only be rescued by coculture of brain samples with Vero cells. Histopathological findings were consistent with the suckling mouse model and with a delayed-type hypersensitivity reaction. XJ inoculation by extraneural routes failed to cause disease, however, it induced Nt Abs. Ic infection with XJCL3 strain of JV attenuated for man and guinea pig, but not for mouse, induced high Nt Ab levels but not mortality. In either case, mice resisted ic XJ challenge. Thus, C3H/HeJ is the first adult mouse model susceptible to JV.
Insights
Researchers discovered that the C3H/HeJ mouse strain is susceptible to Junin virus (JV) infection, developing neurological signs and high mortality. This finding establishes the first adult mouse model for studying JV, crucial for understanding this dangerous pathogen.
Area of Science:
- Virology
- Immunology
- Neurology
Background:
- Adult mice were previously considered resistant to Junin virus (JV) infection.
- Junin virus causes severe disease, including hemorrhagic fever, in humans.
Purpose of the Study:
- To establish a susceptible adult mouse model for Junin virus (JV) infection.
- To investigate the pathological and immunological responses to JV in a susceptible adult mouse model.
Main Methods:
- Intracerebral inoculation of C3H/HeJ mice (up to 5 months old) with the prototype XJ strain of Junin virus.
- Monitoring for neurological signs, mortality, and viral presence via virus isolation.
- Detection of neutralizing antibodies (Nt Ab) and immunofluorescent antibodies.
- Histopathological examination of brain tissues.
- Extraneural inoculation and infection with an attenuated JV strain (XJCL3) for comparative analysis.
Main Results:
- C3H/HeJ mice up to 5 months old exhibited high susceptibility to intracerebral JV inoculation, with 80-90% mortality within 13 days and neurological signs.
- Neutralizing antibodies were absent, but low levels of immunofluorescent antibodies were detected from day +7.
- Virus was recoverable from brain samples by co-culture with Vero cells.
- Histopathology revealed findings consistent with the suckling mouse model and a delayed-type hypersensitivity reaction.
- Extraneural inoculation induced Nt Abs but not disease, while attenuated JV strain (XJCL3) induced high Nt Ab levels without mortality.
- Mice infected with XJCL3 resisted subsequent intracerebral challenge with XJ strain.
Conclusions:
- The C3H/HeJ mouse strain is the first adult mouse model demonstrated to be susceptible to Junin virus (JV) infection.
- This model provides a valuable tool for studying JV pathogenesis, immune responses, and for testing antiviral therapies.
- Intracerebral inoculation is critical for inducing lethal disease in this model, while extraneural routes primarily elicit antibody responses.