Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain
Primary human immunodeficiency virus type 1 viremia and central nervous system invasion in a novel hu-PBL-immunodeficient mouse strain
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DOI：
10.1128/jvi.71.3.2417-2424.1997
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发表时间：
1997-03-01
影响因子：
5.4
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Koyanagi, Y;Tanaka, Y;Yamamoto, N
我们利用NK细胞耗竭抗体建立了四个T、B细胞缺陷和先天免疫反应缺陷的新小鼠品系，并表明所有突变品系都能有效地接受人外周血白细胞(PBL)移植(Hu-PBL-SCID小鼠)。在这些新的HU-PBL-SCID小鼠中观察到比传统的HU-PBL-C.B-L7-SCID小鼠更高水平的人类免疫缺陷病毒1型(HIV-1)复制。在一种特殊的品系HU-PBL-NOD-SCID小鼠中，在感染HIV-1后检测到高水平的HIV-1病毒血症(超过10(6)50%的感染量/毫升)。血浆病毒载量大约是感染HIV-1的其他Hu-PBL-SCID小鼠的100到1000倍。尽管高水平的病毒血症与感染小鼠细胞中HIV-1RNA的总量无关，但只有Hu-PBL-NOD-SCID小鼠才能检测到高水平的游离病毒粒子。HIV-1病毒血症导致全身性HIV-1感染，累及肝脏、肺和脑。PCR原位杂交证实HIV-1感染细胞侵入了Hu-PBL-NOD-SCID小鼠的脑组织。我们的结果表明，遗传背景，包括先天免疫，在原发HIV-1病毒血症和随后的HIV-1入侵中枢神经系统的发展中起关键作用。HU-PBL-NOD-SCID小鼠是研究HIV-1体内致病机制，特别是脑损害和治疗原发HIV-1病毒血症的有效模型。
We established four new mouse strains with defective T and B cells as well as defects in innate immunological reactions using an NK cell depletion antibody and showed that all mutant mouse strains efficiently received human peripheral blood leukocyte (PBL) engraftment (hu-PBL-scid mice). Higher levels of human immunodeficiency virus type 1 (HIV-1) replication were observed in these new hu-PBL-scid mice than in conventional hu-PBL-C.B-l7-scid mice. In one particular strain, hu-PBL-NOD-scid mice, high levels of HIV-1 viremia (more than 10(6) 50% infectious doses per ml) were detected after infection with HIV-1. The plasma viral load was about 100 to 1,000 times higher than that observed in other hu-PBL-scid mice infected with HIV-1. Although high-level viremia did not correlate with the total amount of HIV-1 RNA in cells from infected mice, high levels of free virions were detected only in hu-PBL-NOD-scid mice. HIV-1 viremia induced systemic HIV-1 infection involving the liver, lungs, and brain. PCR in situ hybridization confirmed that HIV-1-infected cells invaded the brain tissue of the hu-PBL-NOD-scid mice. Our results suggest that the genetic background, including innate immunity, is critical in the development of primary HIV-1 viremia and subsequent central nervous system invasion with HIV-1. The hu-PBL-NOD-scid mouse represents a useful model for the study of the pathogenesis of HIV-1 in vivo, especially brain involvement, and therapy of primary HIV-1 viremia.