Mutual functional destruction of HIV-1 Vpu and host TASK-1 channel.
Sequence analysis predicted significant structural homology between the HIV-1 accessory protein Vpu and the N-terminal region of TASK-1, a mammalian background K(+) channel. If the homology resulted from molecular piracy during HIV-1 evolution, these two proteins may have important functional interactions. Here we demonstrate that TASK and Vpu physically interact in cultured cells and in AIDS lymphoid tissues. The functional consequences were potentially destructive for both components: Vpu abolished TASK-1 current, while overexpressing TASK led to a marked impairment of Vpu's ability to enhance viral particle release. Further, the first 40 amino acids of TASK-1 (part of the homology to Vpu) were capable of enhancing HIV-1 particle release. This virus-host interaction may influence HIV-1/AIDS progression, as well as electrical signaling in infected host tissues.
Hsu
Kate
K
Institute of Molecular Cardiobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Seharaseyon
Jegatheesan
J
Dong
Peihong
P
Bour
Stephan
S
Marbán
Eduardo
E
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D016384:Consensus Sequence; D017124:Conserved Sequence; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D011233:Precipitin Tests; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D054334:Viral Regulatory and Accessory Proteins; D044844:beta-Transducin Repeat-Containing Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C420132:potassium channel subfamily K member 3