SEVERE COMBINED IMMUNODEFICIENT MICE ENGRAFTED WITH MACAQUE PERIPHERAL-BLOOD LEUKOCYTES SUPPORT REPLICATION OF SIVSMM

Peripheral blood leukocytes (PBLs) from normal pigtail macaques mere e ngrafted into severe combined immunodeficient C.B-17 scid/scid (SCID) mice to develop a small animal model in which to study and identify ge netic determinants responsible for the acutely lethal disease syndrome induced by SIVsmmPBj14 (SIV-PBj14) in pigtail macaques, In vivo infec tion of macaques with Sn7-PBj14 results in acute disease in all animal s and death of most animals, depending on the route of infection, due to immune activation and production of inflammatory cytokines, A small animal model in which a similar acute disease syndrome was induced wo uld facilitate screening of virus variants to identify regions of the SIV-PBj14 genome responsible for the unique phenotype, Although intrap eritoneal inoculation of SCID mice with SIV-PBj14-infected PBLs or uni nfected PBLs followed by cell-free SIV-PBj14 produced chimeric mac-PBL -SCID mice that supported SIV replication, obvious clinical signs of d isease were not observed, SIV-infected macaque PBLs were recovered fro m spleen, bone marrow, peripheral blood, and the peritoneal cavity; ce ll-free SIV was recovered from peritoneal lavage fluid and serum or pl asma, PBLs that were mitogen stimulated and SIV-PBj14 infected in vitr o migrated rapidly and were recovered from the spleen and bone marrow as early as 1 day after inoculation of mice, The mac-PBL-SCID model ma y be useful for screening potential drug or immunomodulatory therapies before testing in macaques.