In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-01-23)
Abstract:
Viruses are miniscule parasites that hijack the resources of a cell to make more of themselves. For many, this involves getting inside the nucleus, the fortress that protects the cell’s genetic information. To do so, viruses need to first find a way through a double-layered membrane called the nuclear envelope, which only opens up when a cell divides. Yet, the human immunodeficiency virus type 1 (HIV-1) can infect cells that no longer divide, and in which the nucleus’ walls never come down. The virus cores then head for the nuclear pores, heavily guarded holes in the nuclear envelope that allow the cell's own molecules to go in and out of the nucleus. But HIV-1 is too big to fit through, as its genetic information is encased in a capsid, a coat made of a complex assembly of proteins. However, research shows that these capsid proteins can bind to host proteins at the pore or even inside the nucleus. For example, the capsid protein can recognize the pore protein Nup153, or the nuclear protein CPSF6. These interactions could help the virus make its way in, but how these events unfold is still unclear. To explore this, Bejarano, Peng et al. attached fluorescent labels to HIV-1 and watched as it infected non-dividing cells. Rather than completely get rid of their capsid before they crossed the pores, the virus particles hung on to a large part of their lattice. This remaining coat then attached to CPSF6; when this protein was missing or could not bind to capsid proteins, the viral complexes got stuck in the nuclear pores. This suggests that the capsid lattice could first interact with Nup153 inside the pores: then, CPSF6 would take over, knocking Nup153 away and pulling HIV-1 into the nucleus. Armed with this knowledge, virologists and drug developers could try to block HIV-1 from entering the cell’s nucleus; they could also start to dissect how drugs that target the HIV-1 capsid work. Ultimately, HIV-1 may serve as a model to unravel how large objects can pass the nuclear pore, which may help us understand how molecules are constantly trafficked in and out of the nucleus.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.41800.001
DOI:
10.7554/eLife.41800.002
DOI:
10.7554/eLife.41800.003
DOI:
10.7554/eLife.41800.007
DOI:
10.7554/eLife.41800.004
DOI:
10.7554/eLife.41800.005
DOI:
10.7554/eLife.41800.006
DOI:
10.7554/eLife.41800.008
DOI:
10.7554/eLife.41800.009
DOI:
10.7554/eLife.41800.010
DOI:
10.7554/eLife.41800.011
DOI:
10.7554/eLife.41800.012
DOI:
10.7554/eLife.41800.015
DOI:
10.7554/eLife.41800.013
DOI:
10.7554/eLife.41800.016
DOI:
10.7554/eLife.41800.014
DOI:
10.7554/eLife.41800.017
DOI:
10.7554/eLife.41800.018
DOI:
10.7554/eLife.41800.020
DOI:
10.7554/eLife.41800.019
DOI:
10.7554/eLife.41800.021
DOI:
10.7554/eLife.41800.022
DOI:
10.7554/eLife.41800.023
DOI:
10.7554/eLife.41800.024
DOI:
10.7554/eLife.41800.025
DOI:
10.7554/eLife.41800.026
DOI:
10.7554/eLife.41800.027
DOI:
10.7554/eLife.41800.028
DOI:
10.7554/eLife.41800.030
DOI:
10.7554/eLife.41800.031
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3
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