Taruishi Midori, Yoshimatsu Kumiko, Araki Koichi, Okumura Megumi, Nakamura Ichiro, Kajino Kiichi, Arikawa Jiro
Institute for Animal Experimentation, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Sapporo 060-8638, Japan.
Virology. 2007 Sep 1;365(2):292-301. doi: 10.1016/j.virol.2007.02.039. Epub 2007 May 3.
The major histocompatibility complex (MHC) class-I restricted epitope of Hantaan virus nucleocapsid protein (N) was identified using overlapping peptides and BALB/c mice. Using the MHC tetramer derived from the epitope, we found that the level of N-specific CD8(+) T cells increased to approximately 20% of all antigen-specific CD8(+) T cells in a mouse model of transient infection. However, N-specific CD8(+) T cells were undetectable in a mouse model of persistent infection, both in the persistently infected phase and in the convalescent phase. Levels of CD8(+) T cells producing interferon-gamma were weak in both the acute and convalescent phases in the persistently infected model. These results indicate that hantavirus strongly suppresses the production of N-specific CD8(+) T cells throughout the course of infection in persistently infected mice. Moreover, N-specific CD8(+) T cells were not effective in recovering persistently infected mice, despite the existence of abundant N antigen in vivo.
利用重叠肽段和BALB/c小鼠鉴定了汉坦病毒核衣壳蛋白(N)的主要组织相容性复合体(MHC)I类限制性表位。使用源自该表位的MHC四聚体,我们发现在短暂感染的小鼠模型中,N特异性CD8(+) T细胞水平增加至所有抗原特异性CD8(+) T细胞的约20%。然而,在持续感染的小鼠模型中,无论是在持续感染阶段还是恢复期,均未检测到N特异性CD8(+) T细胞。在持续感染模型的急性期和恢复期,产生干扰素-γ的CD8(+) T细胞水平均较弱。这些结果表明,在持续感染的小鼠中,汉坦病毒在整个感染过程中强烈抑制N特异性CD8(+) T细胞的产生。此外,尽管体内存在大量N抗原,但N特异性CD8(+) T细胞在恢复持续感染的小鼠方面无效。