We propose to construct a CCR2b-tropic recombinant SIV (rSIV) to study its transmission and pathogenesis in macaques. This proposal is based on our recent finding of a unique SIVrcm strain in West Africa. Because SIVrcm is the only primate lentivirus identified thus far that uses neither CCR5 nor CXCR4 but CCR2b as a coreceptor, we plan to further study the function of the viral envelope in vivo. First, we will construct an rSIVrcm by replacing the env gene of the pathogenic molecular clone SIVmac239 with the counterpart of SIVrcm. Second, we will compare the biological properties of the rSIVrcm to its parental SIVrcm and SIVmac239 strains. Third, we will study viral transmission and pathogenesis after inoculating a replication-competent rSIVrcm into macaques via vaginal, rectal and intravenous routes. For the latter, we will determine: 1) which route will confer productive infection and if the transmission is mediated by CD4+/CCR2+ cells; 2) changes in biological and genetic properties of the recovered virus through transmission and over time; 3) viral dissemination and tropism; 4) pathological effects in peripheral cells and lymph tissues using flow cytometry, immunohistochemistry and in situ hybridization techniques; 5) correlation between viral load and disease development using a quantitative PCR assay; and 6) clinical signs of AIDS-like disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI010256-01
Application #
2774557
Study Section
Special Emphasis Panel (ZRG5-AARR-1 (01))
Program Officer
Sager, Polly R
Project Start
1999-02-01
Project End
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016