Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat.
A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS.
Buonocore
L
L
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Rose
J K
JK
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy; D005822:Genetic Vectors; D016655:HIV Core Protein p24 / Q000032:analysis / Q000096:biosynthesis; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015183:Restriction Mapping; D016176:T-Lymphocyte Subsets / Q000382:microbiology / Q000502:physiology*; D014779:Virus Replication
D015704:CD4 Antigens; D016655:HIV Core Protein p24