1. Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type I interferon induction
- Author
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Arevik Mosoian, Avelino Teixeira, Eric E. Schadt, Benjamin Yen, Christopher F. Basler, Gabriele Luca Gusella, Albert G. Thomas, Judith A. Aberg, Yujin Hoshida, Xintong Chen, Michael P. Mullen, Harm van Bakel, and Adolfo García-Sastre
- Subjects
Anti-HIV Agents ,Molecular Sequence Data ,Biology ,CD8-Positive T-Lymphocytes ,Prothymosin Alpha ,Virus Replication ,Major Articles and Brief Reports ,Interferon ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,Amino Acid Sequence ,Protein Precursors ,Cells, Cultured ,Regulation of gene expression ,Innate immune system ,Interleukins ,Macrophages ,Small acidic protein ,Interferon-beta ,Virology ,Molecular biology ,Body Fluids ,Thymosin ,Infectious Diseases ,Gene Expression Regulation ,Interferon Type I ,HIV-1 ,Female ,Interferons ,CD8 ,Interferon type I ,medicine.drug - Abstract
Soluble factors from CD8(+) T cells and cervicovaginal mucosa of women are recognized as important in controlling human immunodeficiency virus type 1 (HIV-1) infection and transmission. Previously, we have shown the strong anti-HIV-1 activity of prothymosin α (ProTα) derived from CD8(+) T cells. ProTα is a small acidic protein with wide cell distribution, to which several functions have been ascribed, depending on its intracellular or extracellular localization. To date, activities of ProTα have been attributed to a single protein known as isoform 2. Here we report the isolation and identification of 2 new ProTα variants from CD8(+) T cells and cervicovaginal lavage with potent anti-HIV-1 activity. The first is a splice variant of the ProTα gene, known as isoform CRA_b, and the second is the product of a ProTα gene, thus far classified as a pseudogene 7. Native or recombinant ProTα variants potently restrict HIV-1 replication in macrophages through the induction of type I interferon. The baseline expression of interferon-responsive genes in primary human cervical tissues positively correlate with high levels of intracellular ProTα, and the knockdown of ProTα variants by small interfering RNA leads to downregulation of interferon target genes. Overall, these findings suggest that ProTα variants are innate immune mediators involved in immune surveillance.
- Published
- 2014