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Immunogenic determinants of a neuropathogenic murine leukemia virus
D S Robbins1, M P Remington, M Sarzotti
1Research Service, Department of Veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
Abstract:
Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection demonstrated that cytotoxic T cells (CTL) of the CD8+ phenotype play a role in resistance to the neuropathogenic effects of the virus in NFS/N mice. In the current study, we sought to identify the Cas-MuLV epitopes that are immunogenic for the CTL response. Infection of adult NFS/N mice with a well-characterized neuropathogenic variant of Friend MuLV, PVC-211 MuLV (PVC-MuLV), was not immunogenic for MuLV-specific CTL. Therefore, we constructed chimeric viruses between Cas-MuLV and PVC-MuLV. Infectious chimeras contained the Cas-MuLV env gene on a PVC-MuLV background (PVC-CasenvMuLV) and the PVC-MuLV env gene on a Cas-MuLV background (Cas-PVCenvMuLV). Cas-MuLV-specific CTL were found following inoculation of both the chimeric viruses and the parental Cas-MuLV but not the parental PVC-MuLV, despite evidence of antibody responses to both parental and chimeric MuLV. CTL generated in response to infection with PVC-CasenvMuLV and Cas-PVCenvMuLV were exclusively of the CD8+ phenotype. These results indicate that both the env and gag-pol regions of Cas-MuLV express epitopes that are immunogenic for CTL.
Insights
Cytotoxic T cells (CTL) target specific regions of Cas-Br-M murine leukemia virus (MuLV). These findings identify Cas-MuLV env and gag-pol epitopes crucial for CTL-mediated immune responses against viral neuropathogenesis.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Cytotoxic T cells (CTL) of the CD8+ phenotype are known to confer resistance to the neuropathogenic effects of Cas-Br-M murine leukemia virus (MuLV) in NFS/N mice.
- Identifying specific viral epitopes recognized by CTL is crucial for understanding immune responses to MuLV infection.
Purpose of the Study:
- To identify Cas-MuLV epitopes that are immunogenic for the CTL response.
- To investigate the role of viral env and gag-pol genes in eliciting CTL immunity.
Main Methods:
- Construction of chimeric viruses between Cas-MuLV and a neuropathogenic variant, PVC-MuLV.
- Inoculation of NFS/N mice with parental and chimeric MuLV strains.
- Analysis of CTL responses, including phenotype and epitope specificity.
Main Results:
- Cas-MuLV infection and chimeric virus inoculation elicited MuLV-specific CTL responses, whereas PVC-MuLV did not.
- CTL generated were exclusively of the CD8+ phenotype.
- Antibody responses were observed for both parental and chimeric MuLV, but only Cas-MuLV and chimeras induced CTL.
Conclusions:
- Both the env and gag-pol regions of Cas-MuLV express epitopes that are immunogenic for CTL.
- These identified epitopes are important for CTL-mediated resistance to MuLV neuropathogenesis.