TY - JOUR
T1 - Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type i interferon induction
AU - Teixeira, Avelino
AU - Yen, Benjamin
AU - Gusella, Gabriele Luca
AU - Thomas, Albert G.
AU - Mullen, Michael P.
AU - Aberg, Judith
AU - Chen, Xintong
AU - Hoshida, Yujin
AU - Van Bakel, Harm
AU - Schadt, Eric
AU - Basler, Christopher F.
AU - García-Sastre, Adolfo
AU - Mosoian, Arevik
N1 - Publisher Copyright:
© 2014 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - Cervicovaginal lavage
KW - HIV-1
KW - Macrophages
KW - Prothymosin alpha
UR - http://www.scopus.com/inward/record.url?scp=84928905808&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiu643
DO - 10.1093/infdis/jiu643
M3 - Article
C2 - 25404520
AN - SCOPUS:84928905808
SN - 0022-1899
VL - 211
SP - 1467
EP - 1475
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -