Structural basis for spumavirus GAG tethering to chromatin
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A–H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA). Substitutions of the invariant arginine anchor residue in GAG result in global redistribution of PFV and macaque simian foamy virus (SFVmac) integration sites toward centromeres, dampening the resulting proviral expression without affecting the overall efficiency of integration. Our findings underscore the importance of retroviral structural proteins for integration site selection and the avoidance of genomic junkyards.
Date Issued
2017-05-23
Date Acceptance
2017-04-19
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (21), pp.5509-5514
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
5509
End Page
5514
Journal / Book Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume
114
Issue
21
Copyright Statement
© 2017 The Author(s). Freely available online through the PNAS open access option.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000401797800061&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
retrovirus
integration
nucleosome
chromatin-binding
LEUKEMIA-VIRUS INTEGRATION
FOAMY VIRUS
HIV-1 INTEGRATION
RETROVIRAL INTEGRATION
LEDGF/P75 INTERACTS
HUMAN GENOME
P12 PROTEIN
NUCLEOSOME
TRANSCRIPTION
TARGETS
chromatin-binding
integration
nucleosome
retrovirus
Histones
Nucleosomes
Spumavirus
Virus Integration
Nucleosomes
Spumavirus
Histones
Virus Integration
Publication Status
Published
Date Publish Online
2017-05-10