Processing, secretion, and anti-HIV-1 activity of IL-16 with or without a signal peptide in CD4+ T cells.
CD4+ T cells transfected with the C-terminal 130 aa of human IL-16 are rendered resistant to HIV infection. Whether the constitutively expressed IL-16 acts intracellularly, extracellularly, or both is not clear. To address this question and to further study the processing of IL-16, new constructs containing either the C-terminal 130 aa or the C-terminal 100 aa (PDZ-like motif) were constructed with and without a signal peptide. Pulse-chase experiments and treatment of cells with brefeldin A and/or tunicamycin showed that IL-16 is secreted despite the absence of a signal peptide, but with a signal peptide IL-16 is processed through the endoplasmic reticulum-golgi pathway and is glycosylated. Cells expressing IL-16 linked to a signal peptide secrete considerably more IL-16 into the supernatant than cells expressing IL-16 without a signal peptide and are considerably more resistant to HIV replication. Resistance extends to almost 25 days for cells expressing IL-16 with signal peptide as compared with only 15 days for cells without signal peptide. Cells expressing the C-terminal 100 aa not linked to a signal peptide are poor secretors of IL-16 and show little if any resistance to HIV. In contrast, cells expressing the C-terminal 100 aa linked to a signal peptide secrete IL-16 and are resistant to HIV replication. It is concluded that the secretion of IL-16 is required for HIV inhibition.
Experimental Medicine Section, Oral Infection and Immunity Branch, National Institute of Dental Research, Bethesda, MD 20892, USA.
P
P
Zhou
K
K
Devadas
D
D
Tewari
A
A
Jegorow
A L
AL
Notkins
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000096:biosynthesis; D000998:Antiviral Agents / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000138:chemical synthesis; D006031:Glycosylation; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D019410:Interleukin-16 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000276:immunology*; D021382:Protein Sorting Signals / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D014779:Virus Replication / Q000276:immunology
D000596:Amino Acids; D000998:Antiviral Agents; D019410:Interleukin-16; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins