Identification of amino acids in the human tetherin transmembrane domain responsible for HIV-1 Vpu interaction and susceptibility.
Tetherin, also known as BST-2/CD317/HM1.24, is an antiviral cellular protein that inhibits the release of HIV-1 particles from infected cells. HIV-1 viral protein U (Vpu) is a specific antagonist of human tetherin that might contribute to the high virulence of HIV-1. In this study, we show that three amino acid residues (I34, L37, and L41) in the transmembrane (TM) domain of human tetherin are critical for the interaction with Vpu by using a live cell-based assay. We also found that the conservation of an additional amino acid at position 45 and two residues downstream of position 22, which are absent from monkey tetherins, are required for the antagonism by Vpu. Moreover, computer-assisted structural modeling and mutagenesis studies suggest that an alignment of these four amino acid residues (I34, L37, L41, and T45) on the same helical face in the TM domain is crucial for the Vpu-mediated antagonism of human tetherin. These results contribute to the molecular understanding of human tetherin-specific antagonism by HIV-1 Vpu.
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, 53 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Tomoko
T
Kobayashi
Hirotaka
H
Ode
Takeshi
T
Yoshida
Kei
K
Sato
Peter
P
Gee
Seiji P
SP
Yamamoto
Hirotaka
H
Ebina
Klaus
K
Strebel
Hironori
H
Sato
Yoshio
Y
Koyanagi
D000596:Amino Acids / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D000596:Amino Acids; D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins