Human immunodeficiency virus type 1 infection of neonatal severe combined immunodeficient mice xenografted with human cord blood cells

• Published in: AIDS research and human retroviruses Vol. 10; no. 2; p. 131
• Main Authors: Reinhardt, B, Torbett, B E, Gulizia, R J, Reinhardt, P P, Spector, S A, Mosier, D E
• Format: Journal Article
• Language: English
• Published: United States 01.02.1994
• Subjects: Animals; Animals, Newborn; B-Lymphocytes - immunology; CD3 Complex - immunology; Female; Fetal Blood; Graft vs Host Disease - immunology; HIV Antibodies - immunology; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - isolation & purification; Humans; Leukocyte Transfusion; Lymphocyte Activation; Male; Mice; Mice, SCID - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; Transplantation, Heterologous
• ISSN: 0889-2229
• DOI: 10.1089/aid.1994.10.131

In these studies, neonatal C.B-17 severe combined immunodeficient (nSCID) mice were reconstituted with human cord blood leukocytes (hu-CBLs). The resulting hu-CBL-nSCID mice contained readily detectable human CD3+ T lymphocytes and CD20+ human B cells, and produced substantial levels of human IgM and IgG (including all subclasses). Human cells persisted in lymphoid organs and peripheral blood for at least 8 weeks, and CD4+ T cells outnumbered CD8+ T cells. Engraftment of human cells in peripheral lymphoid organs and blood was much greater than that seen in adult SCID mice grafted with adult peripheral blood leukocytes (PBLs). Hu-CBL-nSCID mice were susceptible to infection with laboratory-adapted and fresh clinical human immunodeficiency virus type 1 (HIV-1) isolates. Following infection with HIV-1, virus could be recovered by the coculture of spleen, lymph node, peritoneal cavity, liver, and plasma samples from hu-CBL-nSCID mice with fresh human peripheral blood mononuclear cells, and proviral copies were detectable following amplification using the polymerase chain reaction (PCR). HIV p24 core antigen levels in hu-CBL-nSCID mouse plasma were consistent with ongoing viral replication and high viral burdens. Rapid CD4+ T cell depletion occurred following infection with laboratory isolates of HIV-1 or a syncytium-inducing clinical isolate, but a non-syncytium-inducing clinical isolate caused expansion of CD8+ T cells, leading to an inversion of the CD4:CD8 ratio with only a transient decrease in CD4+ T cells. These results suggest that the hu-CBL-nSCID mouse system has unique features that mimic certain aspects of pediatric HIV infection, and distinguish it from other animal models of HIV infection, including the related hu-PBL-SCID model.