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Prothymosin ? 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 ? (ProT?) derived from CD8(+) T cells. ProT? 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 ProT? have been attributed to a single protein known as isoform 2. Here we report the isolation and identification of 2 new ProT? variants from CD8(+) T cells and cervicovaginal lavage with potent anti-HIV-1 activity. The first is a splice variant of the ProT? gene, known as isoform CRA_b, and the second is the product of a ProT? gene, thus far classified as a pseudogene 7. Native or recombinant ProT? 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 ProT?, and the knockdown of ProT? variants by small interfering RNA leads to downregulation of interferon target genes. Overall, these findings suggest that ProT? variants are innate immune mediators involved in immune surveillance.

SUBMITTER: Teixeira A

PROVIDER: S-EPMC4425839 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Teixeira Avelino A Yen Benjamin B Gusella Gabriele Luca GL Thomas Albert G AG Mullen Michael P MP Aberg Judith J Chen Xintong X Hoshida Yujin Y van Bakel Harm H Schadt Eric E Basler Christopher F CF García-Sastre Adolfo A Mosoian Arevik A

The Journal of infectious diseases 20141117 9

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 ...[more]

PMID: 25404520

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Dataset Information

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

Publications

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

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