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.
