Title |
TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax
|
---|---|
Published in |
Proceedings of the National Academy of Sciences of the United States of America, February 2015
|
DOI | 10.1073/pnas.1419198112 |
Pubmed ID | |
Authors |
Guangyong Ma, Jun-ichirou Yasunaga, Hirofumi Akari, Masao Matsuoka |
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. |
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Country | Count | As % |
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Japan | 2 | 17% |
United States | 2 | 17% |
Unknown | 8 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 10 | 83% |
Practitioners (doctors, other healthcare professionals) | 1 | 8% |
Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 3% |
Brazil | 1 | 3% |
Unknown | 37 | 95% |
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Readers by professional status | Count | As % |
---|---|---|
Researcher | 12 | 31% |
Student > Bachelor | 6 | 15% |
Student > Master | 6 | 15% |
Student > Ph. D. Student | 6 | 15% |
Professor > Associate Professor | 2 | 5% |
Other | 2 | 5% |
Unknown | 5 | 13% |
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Medicine and Dentistry | 6 | 15% |
Immunology and Microbiology | 5 | 13% |
Neuroscience | 2 | 5% |
Other | 2 | 5% |
Unknown | 6 | 15% |