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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.

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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, JohnsonORCID iD for 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: School of Medicine
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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.