title: TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.
authors: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; and.
authors: Guangyong
authors: G
authors: Ma
authors: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; and mmatsuok@virus.kyoto-u.ac.jp jyasunag@virus.kyoto-u.ac.jp.
authors: Jun-ichirou
authors: J
authors: Yasunaga
authors: Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
authors: Hirofumi
authors: H
authors: Akari
authors: Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan; and mmatsuok@virus.kyoto-u.ac.jp jyasunag@virus.kyoto-u.ac.jp.
authors: Masao
authors: M
authors: Matsuoka
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D016356:Gene Products, tax / Q000037:antagonists & inhibitors* / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000502:physiology*; D008251:Macaca; D015303:Simian T-lymphotropic virus 1 / Q000302:isolation & purification; D051822:T Cell Transcription Factor 1 / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D019562:Viral Load
chemical_list: D016356:Gene Products, tax; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1
keywords: HTLV-1; LEF1; TCF1; Tax
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