Human T cell leukemia virus type 1 tax inhibits innate antiviral signaling via NF-κB-dependent induction of SOCS1

Soratree Charoenthongtrakul, Qinjie Zhou, Noula Shembade, Nicole S. Harhaj, Edward W. Harhaj

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Human T cell leukemia virus type 1 (HTLV-1) inhibits host antiviral signaling pathways although the underlying mechanisms are unclear. Here we found that the HTLV-1 Tax oncoprotein induced the expression of SOCS1, an inhibitor of interferon signaling. Tax required NF-κB, but not CREB, to induce the expression of SOCS1 in T cells. Furthermore, Tax interacted with SOCS1 in both transfected cells and in HTLV-1-transformed cell lines. Although SOCS1 is normally a short-lived protein, in the presence of Tax, the stability of SOCS1 was greatly increased. Accordingly, Tax enhanced the replication of a heterologous virus, vesicular stomatitis virus (VSV), in a SOCS1-dependent manner. Surprisingly, Tax required SOCS1 to inhibit RIG-Idependent antiviral signaling, but not the interferon-induced JAK/STAT pathway. Inhibition of SOCS1 by RNA-mediated interference in the HTLV-1-transformed cell line MT-2 resulted in increased IFN-β expression accompanied by reduced HTLV-1 replication and p19 Gag levels. Taken together, our results reveal that Tax inhibits antiviral signaling, in part, by hijacking an interferon regulatory protein.

Original languageEnglish
Pages (from-to)6955-6962
Number of pages8
JournalJournal of Virology
Volume85
Issue number14
DOIs
StatePublished - Jul 1 2011

Fingerprint

Deltaretrovirus
taxes
Antiviral Agents
Interferons
Transformed Cell Line
interferons
Viruses
Vesicular Stomatitis
Oncogene Proteins
cell lines
Virus Replication
RNA Interference
Vesiculovirus
Proteins
regulatory proteins
crossover interference
T-Lymphocytes
T-lymphocytes
RNA
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

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Human T cell leukemia virus type 1 tax inhibits innate antiviral signaling via NF-κB-dependent induction of SOCS1. / Charoenthongtrakul, Soratree; Zhou, Qinjie; Shembade, Noula; Harhaj, Nicole S.; Harhaj, Edward W.

In: Journal of Virology, Vol. 85, No. 14, 01.07.2011, p. 6955-6962.

Research output: Contribution to journalArticle

Charoenthongtrakul, Soratree ; Zhou, Qinjie ; Shembade, Noula ; Harhaj, Nicole S. ; Harhaj, Edward W. / Human T cell leukemia virus type 1 tax inhibits innate antiviral signaling via NF-κB-dependent induction of SOCS1. In: Journal of Virology. 2011 ; Vol. 85, No. 14. pp. 6955-6962.
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