Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex

详细信息    查看全文

• 作者：Haffar ; Omar K. ; Popov ; Serguei ; Dubrovsky ; Larisa ; Agostini ; Isabelle ; Tang ; Hao ; Pushkarsky ; Tatiana ; et. al.
• 关键词：Vpr/nuclear import ; karyopherin ; pre-integration complex ; PIC ; pre-integration complex ; NLS ; nuclear localization signal ; IN ; integrase ; MA ; matrix protein ; Vpr ; Virus protein R ; NES ; nuclear export signal
• 刊名：Journal of Molecular Biology
• 出版年：2000
• 出版时间：June 2, 2000
• 年：2000
• 卷：299
• 期：2
• 页码：359-368
• 全文大小：286 K

文摘

Replication of HIV-1 in non-dividing and slowly proliferating cell populations depends on active import of the viral pre-integration complex (PIC) into the cell nucleus. While it is commonly accepted that this process is mediated by an interaction between the HIV-1 PIC and the cellular nuclear import machinery, controversial results have been reported concerning the mechanisms of this interaction. Here, we demonstrate that a recently identified nuclear localization signal within the HIV-1 matrix protein (MA), MA NLS-2, together with previously described MA NLS-1, mediates nuclear import of the HIV-1 PIC. Inactivation of both MA NLSs precluded nuclear translocation of MA and rendered the virus defective in nuclear import and replication in non-dividing macrophage cultures, even when functional Vpr and integrase (IN), two more viral proteins implicated in HIV-1 nuclear import, were present. Taken together, these results indicate that Vpr does not function as an independent nuclear import factor and demonstrate that HIV-1 MA, by virtue of its two nuclear localization signals, regulates HIV-1 nuclear import.