title: Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type I interferon induction.
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.
authors.affiliation: Department of Medicine.
authors.forename: Avelino
authors.initials: A
authors.lastname: Teixeira
authors.affiliation: Department of Microbiology.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yen
authors.affiliation: Department of Medicine.
authors.forename: Gabriele Luca
authors.initials: GL
authors.lastname: Gusella
authors.affiliation: Department of Medicine.
authors.forename: Albert G
authors.initials: AG
authors.lastname: Thomas
authors.affiliation: Department of Medicine.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mullen
authors.affiliation: Department of Medicine.
authors.forename: Judith
authors.initials: J
authors.lastname: Aberg
authors.affiliation: Department of Medicine.
authors.forename: Xintong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medicine.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.affiliation: Department of Genetics and Genomics Sciences Icahn Institute for Genomics and Multiscale Biology.
authors.forename: Harm
authors.initials: H
authors.lastname: van Bakel
authors.affiliation: Department of Genetics and Genomics Sciences Icahn Institute for Genomics and Multiscale Biology.
authors.forename: Eric
authors.initials: E
authors.lastname: Schadt
authors.affiliation: Department of Microbiology.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.affiliation: Department of Medicine Department of Microbiology Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Medicine.
authors.forename: Arevik
authors.initials: A
authors.lastname: Mosoian
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology; D001826:Body Fluids / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology; D000095022:Interferon Lambda
chemical_list: D019380:Anti-HIV Agents; D007370:Interferon Type I; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011498:Protein Precursors; D013947:Thymosin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C040782:prothymosin alpha
keywords: CD8+ T cells; HIV-1; cervicovaginal lavage; macrophages; prothymosin alpha