DEVELOPMENT OF TRANSGENIC MICE INFECTABLE WITH HIV1

描述(改编自申请人的摘要)：本报告的目的 研究建议是开发一种小动物模型，更具体地说，一种 HIV-1感染和艾滋病的小鼠模型。像老鼠这样的小动物 不会感染HIV-1，因为它们不携带HIV-1受体， 人类的CD4(HCD4)分子。然而，即使它们表达hCD4，小鼠 细胞不会被HIV-1感染，因为它们缺乏适当的 共同受体。最近对这些共同受体的鉴定使小鼠 培养的细胞在体外可被HIV-1感染。调查人员已经 构建了同时表达hCD4和/或两者的转基因小鼠 共同受体CXCR-4和Ccr-5。他们建议(1)描述这种模式 CXCR-4和CCR-5在这些小鼠中的表达，并鉴定其特异性 表达转基因的细胞亚群；(2)建立实验 体外感染转基因小鼠原代细胞的条件；(3)产生 HIV-1变异体在这些TG的细胞中复制能力增强 在体外和体内的小鼠；以及(4)建立条件以获得 对这些转基因小鼠进行高效感染。

DESCRIPTION (adapted from applicant's abstract): The objective of this research proposal is to develop a small animal model, more specifically, a mouse model of HIV-1 infection and of AIDS. Small animals such as mice are not infectable with HIV-1 because they do not harbor the receptor for HIV-1, the human CD4 (hCD4) molecule. However, even if they express hCD4, mouse cells are not infectable by HIV-1 because they lack an appropriate co-receptor. The recent identification of these co-receptors has made mouse cells in culture infectable by HIV-1 in vitro. The investigators have constructed transgenic mice expressing both hCD4 and one or both of the co-receptors CXCR-4 and CCR-5. They propose to (1) characterize the pattern of CXCR-4 and CCR-5 expression in these mice and to identify the specific subset of cells expressing the transgenes; (2) establish experimental conditions to infect primary cells from these Tg mice in vitro; (3) generate HIV-1 variants with increased capacity to replicate in cells from these Tg mice both in vitro and in vivo; and (4) establish conditions to get productive and efficient infection of these Tg mice.