Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene.
We have generated several transgenic mouse strains carrying a human immunodeficiency virus 1 (HIV-1) NEF/3' long terminal repeat (LTR) transgene under control of a T cell-specific promoter-enhancer element, showing a depletion of CD4+ T cells in the thymus and periphery. The immunological functions of the line with the most dramatic changes in lymphocyte populations, B6/338L, were analyzed in greater detail. The presence of the transgene in the heterozygous animal is associated with a dominant severe immunodeficiency. Older animals develop lymph-adenopathy and splenomegaly. CD4+CD8+ and CD4+CD8- single positive thymocytes already are depleted in these mice at the earliest stages in ontogeny, and peripheral T cells are reduced in frequency and present cell surface marker expression, which is characteristic for memory and activated T cells. The immunological response of B6/338L mice to several viral infections is also greatly impaired. Thus, the HIV-1 NEF/3' LTR as transgene in T cells can cause immunodeficiency and disease with striking similarities to a known retrovirus-induced immunodeficiency called murine AIDS (H. C. Morse III, S. K. Chattopadhyay, M. Makino, T. N. Frederickson, A. W. Hügin, and J. W. Hartley. 1992. AIDS. 6:607).
Lindemann
D
D
Department of Biology, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Wilhelm
R
R
Renard
P
P
Althage
A
A
Zinkernagel
R
R
Mous
J
J
D000375:Aging / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis / Q000276:immunology; D017931:DNA Primers; D005314:Embryonic and Fetal Development / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015754:Genes, nef; D006580:Genetic Carrier Screening; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers