Severe combined immunodeficient mice engrafted with macaque peripheral blood leukocytes support replication of SIVsmm.
Peripheral blood leukocytes (PBLs) from normal pigtail macaques were engrafted into severe combined immunodeficient C.B-17 scid/scid (SCID) mice to develop a small animal model in which to study and identify genetic determinants responsible for the acutely lethal disease syndrome induced by SIVsmmPBj14 (SIV-PBj14) in pigtail macaques. In vivo infection of macaques with SIV-PBj14 results in acute disease in all animals 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 would facilitate screening of virus variants to identify regions of the SIV-PBj14 genome responsible for the unique phenotype. Although intraperitoneal inoculation of SCID mice with SIV-PBj14-infected PBLs or uninfected PBLs followed by cell-free SIV-PBj14 produced chimeric mac-PBL-SCID mice that supported SIV replication, obvious clinical signs of disease were not observed. SIV-infected macaque PBLs were recovered from spleen, bone marrow, peripheral blood, and the peritoneal cavity; cell-free SIV was recovered from peritoneal lavage fluid and serum or plasma. PBLs that were mitogen stimulated and SIV-PBj14 infected in vitro 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 may be useful for screening potential drug or immunomodulatory therapies before testing in macaques.
Schwiebert
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RS
Department of Microbiology, University of Alabama School of Medicine, Birmingham 35294, USA.
Fultz
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PN
D000818:Animals; D001854:Bone Marrow Cells / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005240:Feasibility Studies; D006789:Host vs Graft Reaction; D007074:Immunoglobulin G / Q000097:blood; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000821:virology*; D008254:Macaca nemestrina / Q000097:blood* / Q000821:virology; D051379:Mice; D016513:Mice, SCID / Q000276:immunology / Q000821:virology*; D010529:Peritoneal Cavity / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification / Q000502:physiology*; D013154:Spleen / Q000821:virology; D014779:Virus Replication
D007074:Immunoglobulin G