Panchal Rekha G, Bradfute Steven B, Peyser Brian D, Warfield Kelly L, Ruthel Gordon, Lane Douglas, Kenny Tara A, Anderson Arthur O, Raschke William C, Bavari Sina
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702-5011, USA.
Cell Host Microbe. 2009 Aug 20;6(2):162-73. doi: 10.1016/j.chom.2009.07.003.
Ebola virus (EBOV) infection of humans is a lethal but accidental dead-end event. Understanding resistance to EBOV in other species may help establish the basis of susceptibility differences among its hosts. Although rodents are resistant to EBOV, a murine-adapted variant is lethal when injected intraperitoneally into mice. We find that mice expressing reduced levels of the tyrosine phosphatase CD45 are protected against EBOV, whereas wild-type, CD45-deficient, or enzymatically inactive CD45-expressing mice succumbed to infection. Protection was dependent on CD8(+) T cells and interferon gamma. Reduced CD45-expressing mice retained greater control of gene expression and immune cell proliferation following EBOV infection, which contributed to reduced apoptosis, enhanced viral clearance, and increased protection against the virus. Together, these findings suggest that host susceptibility to EBOV is dependent on the delicate balance of immune homeostasis, which, as demonstrated here, can be determined by the levels of a single regulator.
埃博拉病毒（EBOV）感染人类是一种致命但意外的终末事件。了解其他物种对EBOV的抵抗力可能有助于确立其宿主间易感性差异的基础。尽管啮齿动物对EBOV具有抵抗力，但一种适应小鼠的变体经腹腔注射到小鼠体内时却是致命的。我们发现，表达酪氨酸磷酸酶CD45水平降低的小鼠对EBOV具有抵抗力，而野生型、CD45缺陷型或表达无酶活性CD45的小鼠则会死于感染。抵抗力依赖于CD8(+) T细胞和干扰素γ。表达CD45水平降低的小鼠在感染EBOV后对基因表达和免疫细胞增殖保持更好的控制，这有助于减少细胞凋亡、增强病毒清除并提高对病毒的抵抗力。总之，这些发现表明宿主对EBOV的易感性取决于免疫稳态的微妙平衡，如此处所示，这种平衡可由单一调节因子的水平决定。
