Retroviral integration: Site matters: Mechanisms and consequences of retroviral integration site selection

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integ...

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Published inBioEssays Vol. 37; no. 11; pp. 1202 - 1214
Main Authors Demeulemeester, Jonas, De Rijck, Jan, Gijsbers, Rik, Debyser, Zeger
Format Journal Article
LanguageEnglish
Published United States Published for ICSU Press by Cambridge University Press 01.11.2015
John Wiley and Sons Inc
Subjects
Animals
Capsid - metabolism
DNA, Viral - genetics
HIV Infections - pathology
HIV-1 - genetics
Humans
Integrases - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Leukemia Virus, Murine - genetics
Mice
mutagenicity
nucleosomes
Prospects & Overviews
proviruses
Retroviridae
Retroviridae Infections - pathology
Tumor Virus Infections - pathology
Virus Integration - genetics
Virus Latency - genetics
HIV-1
retrovirus
MLV
cofactor
latency
integration
viral vector
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Abstract Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success.
AbstractList Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success.
Author Demeulemeester, Jonas
Debyser, Zeger
Gijsbers, Rik
De Rijck, Jan
AuthorAffiliation 1 Department of Pharmaceutical and Pharmacological Sciences Laboratory for Molecular Virology and Drug Discovery KU Leuven–University of Leuven Leuven Belgium
2 Department of Pharmaceutical and Pharmacological Sciences Laboratory for Viral Vector Technology and Gene Therapy KU Leuven–University of Leuven Leuven Belgium
3 Department of Chemistry Laboratory for Biomolecular Modeling KU Leuven–University of Leuven Leuven Belgium
AuthorAffiliation_xml – name: 1 Department of Pharmaceutical and Pharmacological Sciences Laboratory for Molecular Virology and Drug Discovery KU Leuven–University of Leuven Leuven Belgium
– name: 2 Department of Pharmaceutical and Pharmacological Sciences Laboratory for Viral Vector Technology and Gene Therapy KU Leuven–University of Leuven Leuven Belgium
– name: 3 Department of Chemistry Laboratory for Biomolecular Modeling KU Leuven–University of Leuven Leuven Belgium
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Issue 11
Keywords HIV-1
retrovirus
MLV
cofactor
latency
integration
viral vector
Language English
License 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
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Snippet Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The...
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SubjectTerms Animals
Capsid - metabolism
DNA, Viral - genetics
HIV Infections - pathology
HIV-1 - genetics
Humans
Integrases - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Leukemia Virus, Murine - genetics
Mice
mutagenicity
nucleosomes
Prospects & Overviews
proviruses
Retroviridae
Retroviridae Infections - pathology
Tumor Virus Infections - pathology
Virus Integration - genetics
Virus Latency - genetics
Title Retroviral integration: Site matters: Mechanisms and consequences of retroviral integration site selection
URI https://www.ncbi.nlm.nih.gov/pubmed/26293289
https://www.proquest.com/docview/2000014518
https://pubmed.ncbi.nlm.nih.gov/PMC5053271
Volume 37
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