CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the plasma membrane upon virus infection.
CD317/Bst-2/tetherin is a host factor that restricts the release of human immunodeficiency virus type 1 (HIV-1) by trapping virions at the plasma membrane of certain producer cells. It is antagonized by the HIV-1 accessory protein Vpu. Previous light microscopy studies localized CD317 to the plasma membrane and the endosomal compartment and showed Vpu induced downregulation. In the present study, we performed quantitative immunoelectron microscopy of CD317 in cells producing wild-type or Vpu-defective HIV-1 and in control cells. Double-labeling experiments revealed that CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network. CD317 largely relocated to endosomes upon HIV-1 infection, and this effect was partly counteracted by Vpu. Unexpectedly, CD317 was enriched in the membrane of viral buds and cell-associated and cell-free viruses compared to the respective plasma membrane, and this enrichment was independent of Vpu. These results suggest that the tethering activity of CD317 critically depends on its density at the cell surface and appears to be less affected by its density in the virion membrane.
Habermann
Anja
A
Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Krijnse-Locker
Jacomine
J
Oberwinkler
Heike
H
Eckhardt
Manon
M
Homann
Stefanie
S
Andrew
Amy
A
Strebel
Klaus
K
Kräusslich
Hans-Georg
HG
D015703:Antigens, CD / Q000032:analysis*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry*; D011992:Endosomes / Q000737:chemistry; D058851:GPI-Linked Proteins; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015497:HIV-1 / Q000737:chemistry*; D054884:Host-Pathogen Interactions; D054298:Human Immunodeficiency Virus Proteins / Q000172:deficiency / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis*; D016253:Microscopy, Immunoelectron; D054334:Viral Regulatory and Accessory Proteins / Q000172:deficiency / Q000502:physiology; D021601:trans-Golgi Network / Q000737:chemistry; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D008562:Membrane Glycoproteins; 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