Robbins D S, Remington M P, Sarzotti M, St Louis D, Hoffman P M
Research Service, Department of Veterans Affairs Medical Center, Baltimore, Maryland 21201, USA.
J Virol. 1995 Nov;69(11):6847-51. doi: 10.1128/JVI.69.11.6847-6851.1995.
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.
先前对卡斯-布伦-墨菲氏鼠白血病病毒(Cas-Br-M MuLV,简称Cas-MuLV)感染的研究表明,CD8+表型的细胞毒性T细胞(CTL)在NFS/N小鼠抵抗该病毒神经致病作用中发挥作用。在本研究中,我们试图鉴定对CTL反应具有免疫原性的Cas-MuLV表位。用特征明确的弗氏鼠白血病病毒神经致病变种PVC-211 MuLV(PVC-MuLV)感染成年NFS/N小鼠,对MuLV特异性CTL不具有免疫原性。因此,我们构建了Cas-MuLV和PVC-MuLV之间的嵌合病毒。有感染性的嵌合体包括在PVC-MuLV背景上携带Cas-MuLV env基因的病毒(PVC-CasenvMuLV)以及在Cas-MuLV背景上携带PVC-MuLV env基因的病毒(Cas-PVCenvMuLV)。尽管有证据表明对亲本和嵌合MuLV均有抗体反应,但接种嵌合病毒和亲本Cas-MuLV后均发现了Cas-MuLV特异性CTL,而接种亲本PVC-MuLV后未发现。由PVC-CasenvMuLV和Cas-PVCenvMuLV感染产生的CTL均为CD8+表型。这些结果表明,Cas-MuLV的env和gag-pol区域均表达对CTL具有免疫原性的表位。