1. Proposed Animal Study to Evaluate Simian Foamy Virus (SFV) Transmission by Blood Arifa S. Khan, Ph.D. DVP, OVRR, CBER, FDA BPAC, December 13, 2001

2. Overall Summary of Planned Study Whole blood from an SFV-infected rhesus macaque will be injected into SFV-negative monkeys. Blood recipients will be monitored for SFV infection by virological, serological, molecular and clinical analysis. The inoculated animals will be followed for 1 year to evaluate SFV infection by blood.

3. Donor Criteria Adult, rhesus macaque from which SFV has been well-characterized (biologically and molecularly). - Exist in-house from previous studies High viral load in plasma and/or PBMCs. - TaqMan PCR for SFV Good replication efficiency. - in vitro analysis in different human cell lines

4. Selection of SFV Negative Animals as Blood Recipients Juvenile, rhesus macaques will be obtained from a known “retrovirus-free” colony and the absence of SRV, STLV and SIV confirmed by independent analysis. SFV negative animals will be identified by serology and confirmed by PCR and culture. Animals will be individually-housed at the time of initial serology and maintained as such throughout study.

5. Experimental Details of Monkey Study to Evaluate SFV Transmission by Blood n Animals [SFV -ve Rhesus macaques] 6 = transfused with SFV + blood 2 = transfused with SFV - blood (controls) n Inoculum: blood volume for intravenous transfusion will be determined according to body weight n Blood Preservative: CPD-adenine (currently used in human blood transfusions) n Plasma and PBMCs will be prepared and stored from every blood collection n Experimentally negative animals will be challenged with a laboratory stock of SFV

6. Monitoring of SFV Infection in Blood Recipients SerologySerology - neutralizing antibody titer - Western blot - Western blot VirologyVirology - SFV detection in monkey PBMCs by PCR and virus identification by sequencing virus identification by sequencing - virus isolation by co-culture of monkey PBMCs - virus isolation by co-culture of monkey PBMCs with Mus dunni cells with Mus dunni cells

7. Additional Evaluation of Monkeys Transfused with SFV + Blood Clinical monitoring - Hematology - Serum chemistry - Serum chemistry - physical exam - physical exam Toxicology Histology Immunophenotyping

8. The results of the proposed study will provide a scientific basis for evaluating potential risk of SFV transmission by blood transfusion and help formulate criteria for acceptance or exclusion of potential blood donors who are at risk for SFV infection.The results of the proposed study will provide a scientific basis for evaluating potential risk of SFV transmission by blood transfusion and help formulate criteria for acceptance or exclusion of potential blood donors who are at risk for SFV infection. STUDY OUTCOME