The Potency of Nef-Mediated SERINC5 Antagonism Correlates with the Prevalence of Primate Lentiviruses in the Wild.

Autor:	Heigele A; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Kmiec D; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Regensburger K; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Langer S; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Peiffer L; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Stürzel CM; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Sauter D; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Peeters M; UMI233, TransVIHMI, Institut de Recherche pour le Développement and Université Montpellier, Montpellier 34394, France., Pizzato M; Virus-Cell Interaction Group, CIBIO, University of Trento, 38123 Povo - Trento, Italy., Learn GH; Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Hahn BH; Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bhahn@upenn.edu., Kirchhoff F; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Electronic address: frank.kirchhoff@uni-ulm.de.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2016 Sep 14; Vol. 20 (3), pp. 381-391.
DOI:	10.1016/j.chom.2016.08.004
Abstrakt:	The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors. Additionally, Nefs of HIV and most SIVs rely on the dileucine motif in the C-terminal loop for anti-SERINC5 activity, while the Nef from colobus SIV (SIVcol) evolved different inhibitory mechanisms. We also found a significant correlation between anti-SERINC5 potency and the SIV prevalence in the respective ape and monkey species. Thus, Nef-mediated SERINC5 antagonism may determine the ability of primate lentiviruses to spread within natural hosts. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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