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Role of the Endocytic Pathway in the Counteraction of BST-2 by Human Lentiviral Pathogens ▿
- Publication Year :
- 2011
- Publisher :
- American Society for Microbiology, 2011.
-
Abstract
- The interferon-inducible transmembrane protein BST-2 (CD317, tetherin) restricts the release of several enveloped viruses from infected cells. BST-2 is broadly active against retroviruses, including HIV-1 and HIV-2. To counteract this host defense, HIV-1 uses the accessory protein Vpu, whereas HIV-2 uses its envelope glycoprotein (Env). In both cases, viral antagonism is associated with decreased expression of BST-2 at the cell surface. Here, we provide evidence supporting a role for the clathrin-mediated endocytic pathway in the downregulation of BST-2 from the cell surface and the counteraction of restricted virion release. A catalytically inactive, dominant negative version of the vesicle “pinch-ase” dynamin 2 (dyn2K44A) inhibited the downregulation of BST-2 by Vpu, and it inhibited the release of wild-type (Vpu-expressing) HIV-1 virions. Similarly, dyn2K44A inhibited the downregulation of BST-2 by HIV-2 Env, and it inhibited the release of vpu -negative HIV-1 virions when HIV-2 Env was provided in trans . dyn2K44A inhibited Env more robustly than Vpu, suggesting that dynamin 2, while a cofactor for both Env and Vpu, might support just one of several pathways though which Vpu counteracts BST-2. In support of a role for clathrin in these effects, the C-terminal domain of the clathrin assembly protein AP180 also inhibited the downregulation of BST-2 by either Vpu or HIV-2 Env. Consistent with modulation of the postendocytic itinerary of BST-2, Vpu enhanced the accumulation of cell surface-derived BST-2 in transferrin-containing endosomes. Vpu also inhibited the transport of BST-2 from a brefeldin A-insensitive compartment to the cell surface, consistent with a block to endosomal recycling. We propose that HIV-1 Vpu, and probably HIV-2 Env, traps BST-2 in an endosomal compartment following endocytosis, reducing its level at the cell surface to counteract restricted viral release.
- Subjects :
- Endosome
viruses
Immunology
Endocytic cycle
Human Immunodeficiency Virus Proteins
Endocytosis
GPI-Linked Proteins
Microbiology
Clathrin
HIV Envelope Protein gp160
Viral envelope
Antigens, CD
Virology
Humans
Viral Regulatory and Accessory Proteins
Dynamin
biology
virus diseases
biochemical phenomena, metabolism, and nutrition
Cell biology
Virus-Cell Interactions
Insect Science
HIV-2
biology.protein
Tetherin
HIV-1
Ap180
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b7fd36c08975b0e87a4fc23ea459daa5