Long-term inhibition of clinical and laboratory human immunodeficiency virus strains in human T-cell lines containing an HIV-regulated diphtheria toxin A chain gene.
The human immunodeficiency virus (HIV) causes persistent infection of T cells. Chemotherapy for infection in humans may slow HIV-related disease progression, but it does not eradicate virus. Thus, other treatment modalities are warranted. We have previously demonstrated that the human T cell line H9, ordinarily permissive for HIV infection, may be protected against infection with the LAI strain of HIV by intracellular immunization with the gene encoding diphtheria toxin A chain (DT-A) under the control of HIV Tat and Rev. Cloned cells were protected for up to 6 days in vitro. We now report protection against the LAI laboratory isolate for up to 59 days, and against clinical HIV strains of differing phenotypic properties and cell tropisms for up to 59 days. In some cases, protection was complete in that no residual HIV was detected by HIV p24 antigen production, co-culture with parental H9 cells, or the polymerase chain reaction (PCR). CD4+ surface expression of DT-A transduced cloned H9 cells was similar to parental H9 in most cases. These results suggest that toxin gene therapy for HIV infection may ultimately be feasible.
Curiel
T J
TJ
University of Colorado Health Sciences Center, Division of Infectious Disease, Denver 80262.
Cook
D R
DR
Wang
Y
Y
Hahn
B H
BH
Ghosh
S K
SK
Harrison
G S
GS
D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D004167:Diphtheria Toxin / Q000235:genetics* / Q000627:therapeutic use; D018274:Electroporation; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D015694:Gene Products, rev / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D016346:Gene Products, vif / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D006801:Humans; D010446:Peptide Fragments / Q000235:genetics* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000382:microbiology*; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D004167:Diphtheria Toxin; D015694:Gene Products, rev; D015696:Gene Products, tat; D016346:Gene Products, vif; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus