title: Ion Channel Activity of Vpu Proteins Is Conserved throughout Evolution of HIV-1 and SIV.
abstract: The human immunodeficiency virus type 1 (HIV-1) protein Vpu is encoded exclusively by HIV-1 and related simian immunodeficiency viruses (SIVs). The transmembrane domain of the protein has dual functions: it counteracts the human restriction factor tetherin and forms a cation channel. Since these two functions are causally unrelated it remains unclear whether the channel activity has any relevance for viral release and replication. Here we examine structure and function correlates of different Vpu homologs from HIV-1 and SIV to understand if ion channel activity is an evolutionary conserved property of Vpu proteins. An electrophysiological testing of Vpus from different HIV-1 groups (N and P) and SIVs from chimpanzees (SIVcpz), and greater spot-nosed monkeys (SIVgsn) showed that they all generate channel activity in HEK293T cells. This implies a robust and evolutionary conserved channel activity and suggests that cation conductance may also have a conserved functional significance.
authors.affiliation: Membrane Biophysics, Technische Universität Darmstadt, 64287 Darmstadt, Germany. timogreiner@googlemail.com.
authors.forename: Timo
authors.initials: T
authors.lastname: Greiner
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, 85764 Oberschleißheim, Germany. sebastian.bolduan@gmx.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bolduan
authors.affiliation: Membrane Biophysics, Technische Universität Darmstadt, 64287 Darmstadt, Germany. Hertelb@bio.tu-darmstadt.de.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hertel
authors.affiliation: Computational Biology & Simulation Group, Deparment of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany. c.gross@bio.tu-darmstadt.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Groß
authors.affiliation: Computational Biology & Simulation Group, Deparment of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany. Hamacher@bio.tu-darmstadt.de.
authors.forename: Kay
authors.initials: K
authors.lastname: Hamacher
authors.affiliation: Institute of Virology, Friedrich Alexander University, 91054 Erlangen, Germany. Ulrich.Schubert@viro.med.uni-erlangen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
authors.affiliation: Department of Biology and CNR IBF-Mi, Università degli Studi di Milano, 20122 Milano, Italy. Anna.moroni@unimi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Moroni
authors.affiliation: Membrane Biophysics, Technische Universität Darmstadt, 64287 Darmstadt, Germany. Thiel@bio.tu-darmstadt.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Thiel
mesh_terms: D002412:Cations / Q000378:metabolism; D002460:Cell Line; D055724:Electrophysiological Phenomena; D015497:HIV-1 / Q000201:enzymology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000201:enzymology*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D002412:Cations; D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: Vpu channel function; Vpu transmembrane domain; viroporin; virus channel evolution