Kyle Jennifer L, Beatty P Robert, Harris Eva
Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
J Infect Dis. 2007 Jun 15;195(12):1808-17. doi: 10.1086/518007. Epub 2007 May 9.
Dengue fever is a mosquitoborne viral illness caused by 4 dengue viruses (DENV-1-4). The cellular tropism of DENV has not been definitively determined, despite its importance for understanding viral pathogenesis and identifying therapeutic targets. To define DENV cellular tropism in a small animal model, 129/Pas mice lacking interferon-alpha/beta and/or-gamma receptors were infected with DENV via a subcutaneous route. During the first week after infection, virus was present in lymph nodes, spleen, bone marrow, and circulating white blood cells. F4/80+CD11b+ macrophages and CD11c+ dendritic cells were demonstrated to be targets for DENV-2 infection in the spleen by flow cytometry directed to structural and nonstructural DENV proteins and by magnetic bead separation followed by strand-specific reverse-transcriptase polymerase chain reaction. We find that the initial cellular tropism of DENV in mice is similar to that reported in humans, thereby paving the way for investigation of cellular tropism and pathogenesis of DENV in primary and secondary infections.
登革热是一种由4种登革病毒(DENV-1-4)引起的蚊媒病毒性疾病。尽管了解登革病毒的细胞嗜性对于理解病毒发病机制和确定治疗靶点很重要,但尚未明确确定其细胞嗜性。为了在小动物模型中定义登革病毒的细胞嗜性,通过皮下途径将缺乏干扰素-α/β和/或-γ受体的129/Pas小鼠感染登革病毒。在感染后的第一周,病毒存在于淋巴结、脾脏、骨髓和循环白细胞中。通过针对登革病毒结构和非结构蛋白的流式细胞术以及磁珠分离后进行链特异性逆转录酶聚合酶链反应,证明F4/80+CD11b+巨噬细胞和CD11c+树突状细胞是脾脏中DENV-2感染的靶细胞。我们发现登革病毒在小鼠中的初始细胞嗜性与人类报道的相似,从而为研究登革病毒在原发性和继发性感染中的细胞嗜性和发病机制铺平了道路。