The C terminus of HIV-1 Tat modulates the extent of CD178-mediated apoptosis of T cells.
HIV infection and the progression to AIDS are characterized by the depletion of CD4(+) T cells through apoptosis of the uninfected bystander cells and the direct killing of HIV-infected cells. This is mediated in part by the human immunodeficiency virus, type 1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells and CD178 gene expression, which is critically involved in T cell apoptosis. The differing ability of HIV strains to induce death of infected and uninfected cells may play a role in the clinical and biological differences displayed by HIV strains. We chemically synthesized the 86-residue truncated short variant of Tat and its full-length form. We show that the trans-activation ability of Tat at the long terminal repeat does not correlate with T cell apoptosis but that the ability of Tat to up-regulate CD178 mRNA expression and induce apoptosis in T cells is critically dependent on the C terminus of Tat. Moreover, the greater 86-residue Tat-induced apoptosis is via the extrinsic pathway of CD95-CD178.
Campbell
Grant R
GR
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California 92093-0672, USA.
Watkins
Jennifer D
JD
Esquieu
Didier
D
Pasquier
Eddy
E
Loret
Erwann P
EP
Spector
Stephen A
SA
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002469:Cell Separation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000737:chemistry* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009154:Mutation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation; D048069:Tumor Necrosis Factors / Q000502:physiology*; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015696:Gene Products, tat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D019014:fas Receptor