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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI042663-02
Application #
2673196
Study Section
Special Emphasis Panel (ZAI1-DET-A (O1))
Project Start
1997-09-30
Project End
1999-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Clinical Research Institute of Montreal
Department
Type
DUNS #
City
Montreal
State
QC
Country
Canada
Zip Code
H2 1-R7