SJL bone marrow-derived macrophages do not have IRF3 mutations and are highly susceptible to Theiler's virus
Kyung-No Son1, Zhiguo Liang1, Howard L Lipton2
1Departments of Microbiology-Immunology, University of Illinois at Chicago, Chicago, IL, USA.
Abstract:
It is well known that SJL mice are susceptible to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease while C57BL6 (B6) and B10 mice are resistant, and H-2s on a B10 background (B10.S) contributes modestly to susceptibility. A recent study linked two IRF3 non-conservative mutations in SJL compared to B10.S mice to resistance to TMEV infection of SJL peritoneal-derived macrophages, an observation of practical interest in light of the central role of IRF3 transcription factor in the type I interferon (IFN) response. However, we did not find these non-conservative mutations among SJL, B10.S, B6 and B10 mice in the IRF3 amino acid sequence, and show SJL bone marrow-derived macrophages infected with TMEV exhibit increased virus RNA replication and infectious virus yields as well as greater IL-6 production than C57Bl strain (including B10.S) cultures.
Insights
SJL mice exhibit higher susceptibility to Theiler's murine encephalomyelitis virus (TMEV) infection, showing increased viral replication and IL-6 production. This contrasts with resistant C57BL6 strains, suggesting a complex genetic basis for TMEV disease.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- SJL mice are susceptible to TMEV-induced demyelinating disease, while C57BL6 (B6) and B10 mice are resistant.
- Previous research suggested IRF3 mutations in SJL mice contributed to TMEV resistance in macrophages.
- The interferon regulatory factor 3 (IRF3) transcription factor is crucial for the type I interferon (IFN) response.
Purpose of the Study:
- To investigate the genetic basis of TMEV susceptibility in SJL mice.
- To re-evaluate the role of IRF3 mutations in TMEV infection of macrophages.
- To compare TMEV replication and IL-6 production in SJL and C57BL6-derived macrophages.
Main Methods:
- Comparing amino acid sequences of IRF3 in SJL, B10.S, B6, and B10 mice.
- Infecting SJL and C57Bl strain (including B10.S) bone marrow-derived macrophages with TMEV.
- Quantifying viral RNA replication and infectious virus yields.
- Measuring IL-6 production in infected macrophage cultures.
Main Results:
- No non-conservative IRF3 mutations were found in SJL mice compared to B10.S, B6, and B10 strains.
- SJL bone marrow-derived macrophages showed increased TMEV RNA replication and infectious virus yields compared to C57Bl strains.
- Greater IL-6 production was observed in TMEV-infected SJL macrophages than in C57Bl strain macrophages.
Conclusions:
- The previously proposed IRF3 mutations do not explain the observed differences in TMEV susceptibility.
- SJL macrophages are intrinsically more permissive to TMEV replication and elicit a stronger IL-6 response.
- Further research is needed to identify the genetic factors underlying SJL mouse susceptibility to TMEV.
