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Direct Visualization of HIV-1 Replication Intermediates Shows that Capsid and CPSF6 Modulate HIV-1 Intra-nuclear Invasion and Integration

Chin, Christopher R.
Perreira, Jill
Savidis, George
Portmann, Jocelyn M.
Aker, Aaron M.
Feeley, Eric M.
Smith, Miles C.
Brass, Abraham L.
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Abstract

Direct visualization of HIV-1 replication would improve our understanding of the viral life cycle. We adapted established technology and reagents to develop an imaging approach, ViewHIV, which allows evaluation of early HIV-1 replication intermediates, from reverse transcription to integration. These methods permit the simultaneous evaluation of both the capsid protein (CA) and viral DNA genome (vDNA) components of HIV-1 in both the cytosol and nuclei of single cells. ViewHIV is relatively rapid, uses readily available reagents in combination with standard confocal microscopy, and can be done with virtually any HIV-1 strain and permissive cell lines or primary cells. Using ViewHIV, we find that CA enters the nucleus and associates with vDNA in both transformed and primary cells. We also find that CA's interaction with the host polyadenylation factor, CPSF6, enhances nuclear entry and potentiates HIV-1's depth of nuclear invasion, potentially aiding the virus's integration into gene-dense regions.

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Chin CR, Perreira JM, Savidis G, Portmann JM, Aker AM, Feeley EM, Smith MC, Brass AL. Direct Visualization of HIV-1 Replication Intermediates Shows that Capsid and CPSF6 Modulate HIV-1 Intra-nuclear Invasion and Integration. Cell Rep. 2015 Nov 24;13(8):1717-31. doi:10.1016/j.celrep.2015.10.036. Epub 2015 Nov 12. PubMed PMID: 26586435. Link to article on publisher's website

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DOI
10.1016/j.celrep.2015.10.036
PubMed ID
26586435
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<p>© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (<a href="http://creativecommons.org/licenses/by-nc-nd/4.0/" target="_blank">http://creativecommons.org/licenses/by-nc-nd/4.0/</a>).</p>