Ion Channel Activity of Vpu Proteins Is Conserved Throughout Evolution of HIV-1 and SIV

Viruses. 2016 Dec 1;8(12):325. doi: 10.3390/v8120325.

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.

Keywords: Vpu channel function; Vpu transmembrane domain; viroporin; virus channel evolution.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cations / metabolism
  • Cell Line
  • Electrophysiological Phenomena
  • HIV-1 / enzymology*
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Humans
  • Ion Channels / metabolism*
  • Simian Immunodeficiency Virus / enzymology*
  • Viral Regulatory and Accessory Proteins / metabolism*

Substances

  • Cations
  • Human Immunodeficiency Virus Proteins
  • Ion Channels
  • Viral Regulatory and Accessory Proteins
  • vpu protein, Human immunodeficiency virus 1