Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1 Costa, Luciana J., Zheng, Yong-Hui, Sabotic, Jerica, Mak, Johnson, Fackler, Oliver T. and Peterlin, B. Matija 2004, Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1, Journal of virology, vol. 78, no. 10, pp. 5311-5323, doi: 10.1128/JVI.78.10.5311-5323.2004. Attached Files Name Description MIMEType Size Downloads mak-nefbinds-2004.pdf Published version application/pdf 2.73MB 453 Title Nef binds p6* in gagpol during replication of human immunodeficiency virus type 1 Author(s) Costa, Luciana J. Zheng, Yong-Hui Sabotic, Jerica Mak, Johnson orcid.org/0000-0002-5229-5707 Fackler, Oliver T. Peterlin, B. Matija Journal name Journal of virology Volume number 78 Issue number 10 Start page 5311 End page 5323 Total pages 13 Publisher American Society for Microbiology Place of publication Washington, D. C. Publication date 2004-05 ISSN 0022-538X 1098-5514 Keyword(s) CD8 antigen gag protein hybrid protein Nef protein Pol protein Summary The atypical Nef protein (NefF12) from human immunodeficiency virus type 1 strain F12 (HIV-1F12) interferes with virion production and infectivity via a mysterious mechanism. The correlation of these effects with the unusual perinuclear subcellular localization of NefF12 suggested that the wild-type Nef protein could bind to assembly intermediates in late stages of viral replication. To test this hypothesis, Nef from HIV-1NL4-3 was fused to an endoplasmic reticulum (ER) retention signal (NefKKXX). This mutant NefKKXX protein recapitulated fully the effects of NefF12 on Gag processing and virion production, either alone or as a CD8 fusion protein. Importantly, the mutant NefKKXX protein also localized to the intermediate compartment, between the ER and the trans-Golgi network. Furthermore, Nef bound the GagPol polyprotein in vitro and in vivo. This binding mapped to the C-terminal flexible loop in Nef and the transframe p6* protein in GagPol. The significance of this interaction was demonstrated by a genetic assay in which the release of a mutant HIV-1 provirus lacking the PTAP motif in the late domain that no longer binds Tsg101 was rescued by a Nef.Tsg101 chimera. Importantly, this rescue as well as incorporation of Nef into HIV-1 virions correlated with the ability of Nef to interact with GagPol. Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1. Language eng DOI 10.1128/JVI.78.10.5311-5323.2004 Field of Research 119999 Medical and Health Sciences not elsewhere classified Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category C1.1 Refereed article in a scholarly journal Copyright notice ©2004, American Society for Microbiology Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30047538 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Thu, 30 Aug 2012, 09:41:05 EST Thu, 30 Aug 2012, 10:37:58 EST Tue, 18 Sep 2012, 13:53:11 EST Tue, 18 Sep 2012, 13:54:19 EST Tue, 18 Sep 2012, 13:55:28 EST Fri, 31 Jan 2014, 09:12:21 EST Fri, 13 Jun 2014, 15:09:02 EST Tue, 06 Sep 2016, 19:37:35 EST Tue, 05 Dec 2017, 12:35:24 EST Fri, 07 Sep 2018, 16:08:23 EST Filtered Full Citation counts:   Cited 26 times in TR Web of Science Cited 28 times in Scopus Search Google Scholar Access Statistics: 555 Abstract Views, 454 File Downloads  -  Detailed Statistics Created: Thu, 30 Aug 2012, 09:41:05 EST