Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type i interferon induction

Avelino Teixeira, Benjamin Yen, Gabriele Luca Gusella, Albert G. Thomas, Michael P. Mullen, Judith Aberg, Xintong Chen, Yujin Hoshida, Harm Van Bakel, Eric Schadt, Christopher F. Basler, Adolfo García-Sastre, Arevik Mosoian

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1467-1475
Number of pages9
JournalJournal of Infectious Diseases
Volume211
Issue number9
DOIs
Publication statusPublished - May 1 2015
Externally publishedYes

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Keywords

  • CD8 T cells
  • Cervicovaginal lavage
  • HIV-1
  • Macrophages
  • Prothymosin alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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