The implication of NMD disruption by HTLV-1 infection in cellular transformation

HTLV-1 感染破坏 NMD 对细胞转化的影响

• 批准号: 22700863
• 负责人: NAKANO Kazumi
• 金额: $ 2.58万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22700863/
• 关键词: がん遺伝子; ヒト白血病ウィルス; HTLV-1; ATL; NMD; ウイルス自己複製; ウイルスゲノムRNA

In the present study, we demonstrated that HTLV-1 infection induces the suppression of the host NMD activity, and that HTLV-1 Rex, the viral post-transcriptional regulator, is responsible for the NMD inhibition. Overexpression of Rex resulted in decreased NMD activity and increased stability of the viral genomic RNA. Moreover, Rex stabilized a native NMD target mRNA, such as nik mRNA. These results suggest that NMD inhibition by Rex is beneficial for the viral replication, but also can influence on the expression levels of aberrant mRNAs as well as native mRNAs targeted by NMD. We demonstrated that HTLV-1 infected T-cell lines have lower NMD activities than HTLV-1 uninfected T-cell lines. Also, gene expression microarray analyses showed that PBMCs from ATL patients have elevated NMD target mRNAs compared with those from healthy donors. Taken together, these results proposed a possibility that NMD disruption by Rex at the time of HTLV-1 infection may implicate in the immortalization and transformation of infected cells.

在本研究中，我们证明了HTLV-1感染诱导了宿主NMD活性的抑制，并且病毒后转录调节剂HTLV-1 REX负责NMD抑制。 REX的过表达导致NMD活性降低和病毒基因组RNA的稳定性提高。此外，雷克斯（Rex）稳定了天然的NMD靶mRNA，例如Nik mRNA。这些结果表明，REX抑制NMD对病毒复制是有益的，但也可能影响NMD靶向的异常mRNA和天然mRNA的表达水平。我们证明了HTLV-1感染的T细胞线的NMD活性低于HTLV-1未感染的T细胞系。此外，基因表达微阵列分析表明，与健康捐助者相比，来自ATL患者的PBMC升高NMD靶标​​mRNA。综上所述，这些结果表明，HTLV-1感染时REX的NMD破坏可能与感染细胞的永生化和转化有关。

项目成果

A Novel Function of HTLV-1 REX in Inhibition of the Host mRNA Surveillance Mechanism (NMD) for Protection of the Viral Genomic mRNA

HTLV-1 REX 抑制宿主 mRNA 监视机制 (NMD) 保护病毒基因组 mRNA 的新功能

• 发表时间: 2011
• 作者: Nakano K;Ando T;Ishida T;Ohsugi T;Tanaka Y;Watanabe T
• 通讯作者: Watanabe T

A Novel Function of HTLV-1 Rex in Inhibition of the Host mRNA Surveillance Mechanism(NMD) for Protection of the Viral Genomic mRNA

HTLV-1 Rex 抑制宿主 mRNA 监视机制 (NMD) 保护病毒基因组 mRNA 的新功能

• 发表时间: 2011
• 作者: Nakano K;Ando T;Yamagishi M;Ishida T;Ohsugi T;Tanaka Y;Brighty D;Watanabe T
• 通讯作者: Watanabe T

HTLV-1 Rexの新しい機能:宿主Nonsense-Mediated mRNA Decay(NMD)の抑制

HTLV-1 Rex的新功能：抑制宿主无义介导的mRNA衰变（NMD）

• 发表时间: 2010
• 作者: Nakano K;Ando T;Ishida T;Ohsugi T;Tanaka Y;Watanabe T
• 通讯作者: Watanabe T

A Novel Function of HTLV-1 Rex in Inhibition of the Host NMD, the mRNA Surveillance Mechanism

HTLV-1 Rex 抑制宿主 NMD（mRNA 监视机制）的新功能

• 发表时间: 2010
• 作者: Nakano K;Ando T;Ishida T;Ohsugi T;Tanaka Y;Watanabe T
• 通讯作者: Watanabe T

A Novel Function of HTLV-1 Rex in Inhibition of the Host mRNA Surveillance Mechanism (NMD) for Protection of the Viral Genotnic mRNA

HTLV-1 Rex 抑制宿主 mRNA 监视机制 (NMD) 保护病毒基因组 mRNA 的新功能

• 发表时间: 2011
• 作者: Nakano K;Ando T;Yamagishi M;Ishida T;Ohsugi T;Tanaka Y;Brighty D;Watanabe T
• 通讯作者: Watanabe T