HIV Relies on Host Proteins to Clear the Way to the Nucleus
By LabMedica International staff writers Posted on 06 Jul 2016 |
Image: HIV-1 viral cores (red) accumulate around the cell nucleus (blue) but remain unable to enter following depletion of the motor protein KIF5B (Photo courtesy of Loyola University Chicago).
The ability of HIV to transit the cytoplasm and enter the nucleus of an infected cell was found to depend on the combined activities of two host proteins, the Kinesin-1 motor protein, KIF5B, and the nuclear pore component Nup358.
Following envelope mediated fusion, the HIV-1 nuclear core is released into the cytoplasm of the target cell and undergoes a series of modifications that result in the nuclear import of the viral genome, which ultimately leads to the integration of viral DNA into the host cell genome. Previous studies had found that disruption of microtubules, or depletion of dynein or kinesin motor proteins, perturbed the normal uncoating and trafficking of the viral genome.
In the current study, which was published in the June 21, 2016, online edition of the journal PLOS Pathogens, investigators at Loyola University (Chicago, IL, USA) enhanced the understanding of how HIV infection progresses by showing that the Kinesin-1 motor protein, KIF5B, induced a relocalization of the nuclear pore component Nup358 into the cytoplasm during HIV-1 infection. This relocalization of NUP358 was dependent on the HIV-1 capsid. NUP358 directly associated with viral cores following cytoplasmic translocation.
The interaction between NUP358 and the HIV-1 core was dependent on multiple capsid binding surfaces, as this association was not observed following infection with capsid mutants in which a conserved hydrophobic binding pocket (N74D) or the cyclophilin A binding loop (P90A) was disrupted. KIF5B knockdown also prevented the nuclear entry and infection by HIV-1, but did not exert a similar effect on the N74D or P90A capsid mutants, which do not rely on Nup358 for nuclear import.
Results obtained during these studies revealed a novel role for the microtubule motor protein KIF5B in the nuclear import of the viral genome and identified potential drug therapeutic intervention targets.
Related Links:
Loyola University
Following envelope mediated fusion, the HIV-1 nuclear core is released into the cytoplasm of the target cell and undergoes a series of modifications that result in the nuclear import of the viral genome, which ultimately leads to the integration of viral DNA into the host cell genome. Previous studies had found that disruption of microtubules, or depletion of dynein or kinesin motor proteins, perturbed the normal uncoating and trafficking of the viral genome.
In the current study, which was published in the June 21, 2016, online edition of the journal PLOS Pathogens, investigators at Loyola University (Chicago, IL, USA) enhanced the understanding of how HIV infection progresses by showing that the Kinesin-1 motor protein, KIF5B, induced a relocalization of the nuclear pore component Nup358 into the cytoplasm during HIV-1 infection. This relocalization of NUP358 was dependent on the HIV-1 capsid. NUP358 directly associated with viral cores following cytoplasmic translocation.
The interaction between NUP358 and the HIV-1 core was dependent on multiple capsid binding surfaces, as this association was not observed following infection with capsid mutants in which a conserved hydrophobic binding pocket (N74D) or the cyclophilin A binding loop (P90A) was disrupted. KIF5B knockdown also prevented the nuclear entry and infection by HIV-1, but did not exert a similar effect on the N74D or P90A capsid mutants, which do not rely on Nup358 for nuclear import.
Results obtained during these studies revealed a novel role for the microtubule motor protein KIF5B in the nuclear import of the viral genome and identified potential drug therapeutic intervention targets.
Related Links:
Loyola University
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