Immunogenic determinants of a neuropathogenic murine leukemia virus

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-Cas env MuLV) and the PVC-MuLV env gene on a Cas-MuLV background (Cas-PVC env MuLV). 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-Cas env MuLV and Cas-PVC env MuLV 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. Previous studies of Cas-Br-M murine leukemia virus (MuLV) (Cas-MuLV) infection have demonstrated that immune T cells play a role in resistance to the neuropathogenic effects of the virus (4, 6, 20). CD8 ϩ cytotoxic T cells (CTL) derived from syngeneic mice exposed to Cas-MuLV at 21 days of age conferred resistance to the neuropathogenic effects of Cas-MuLV when transferred into susceptible newborn NFS/N mice (4). However, since protective T-cell immune responses have not been universally demonstrated in mice during the course of other neuropathogenic MuLV infections (5), the Cas-MuLV epitopes immunogenic for CTL induction in adult NFS/N mice may be unique. Since the env sequences have been implicated in the neuropathogenic effects of several MuLV strains (2, 12, 16, 25) and are the least conserved among the MuLV family of retroviruses (17, 20), we focused our attention on the potential immunogenic epitopes within the Cas-MuLV env gene. In this study, chimeric viruses were constructed between Cas-MuLV (10) and PVC 211 MuLV (PVC-MuLV) (12), a neuropathogenic variant of Friend MuLV that did not stimulate the induction of retrovirus-specific CTL. The results of this study demonstrated that Cas-MuLV contains epitopes in the env region and also in the gag-pol region that are immunogenic for CTL in adult NFS/N mice.

Evidence for oxidative damage in a murine leukemia virus-induced neurodegeneration

“…Vitamin E has been shown to stimulate the immune system in HIV-1 disease (Javier et al, 1990) and improve the peripheral clinical immunodeficiency disease in murine AIDS (Wang et al, 1995). However, this is an unlikely explanation, because PVC-MuLV-infected rats do not exhibit an immune response to the virus , immune dysfunction (Robbins et al, 1995), or malnutrition observed in the aforementioned retroviral diseases.…”