Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles
Investigation of the Vpu protein of HIV-1 recently uncovered a novel aspect of the mammalian innate response to enveloped viruses: retention of progeny virions on the surface of infected cells by the interferon-induced, transmembrane and GPI-anchored protein BST-2 (CD317; tetherin). BST-2 inhibits diverse families of enveloped viruses, but how it restricts viral release is unclear. Here, immuno-electron microscopic data indicate that BST-2 is positioned to directly retain nascent HIV virions on the plasma membrane of infected cells and is incorporated into virions. Virion-incorporation was confirmed by capture of infectivity using antibody to the ectodomain of BST-2. Consistent with a direct tethering mechanism, we confirmed that proteolysis releases restricted virions and further show that this removed the ectodomain of BST-2 from the cell surface. Unexpectedly, enzymatic cleavage of GPI anchors did not release restricted virions, weighing against models in which individual BST-2 molecules span the virion and host cell membranes. Although the exact molecular topology of restriction remains unsolved, we suggest that the incorporation of BST-2 into viral envelopes underlies its broad restrictive activity, whereas its relative exclusion from virions and sites of viral assembly by proteins such as HIV-1 Vpu may provide viral antagonism of restriction.
Vyšlo v časopise:
Direct Restriction of Virus Release and Incorporation of the Interferon-Induced Protein BST-2 into HIV-1 Particles. PLoS Pathog 6(3): e32767. doi:10.1371/journal.ppat.1000701
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000701
Souhrn
Investigation of the Vpu protein of HIV-1 recently uncovered a novel aspect of the mammalian innate response to enveloped viruses: retention of progeny virions on the surface of infected cells by the interferon-induced, transmembrane and GPI-anchored protein BST-2 (CD317; tetherin). BST-2 inhibits diverse families of enveloped viruses, but how it restricts viral release is unclear. Here, immuno-electron microscopic data indicate that BST-2 is positioned to directly retain nascent HIV virions on the plasma membrane of infected cells and is incorporated into virions. Virion-incorporation was confirmed by capture of infectivity using antibody to the ectodomain of BST-2. Consistent with a direct tethering mechanism, we confirmed that proteolysis releases restricted virions and further show that this removed the ectodomain of BST-2 from the cell surface. Unexpectedly, enzymatic cleavage of GPI anchors did not release restricted virions, weighing against models in which individual BST-2 molecules span the virion and host cell membranes. Although the exact molecular topology of restriction remains unsolved, we suggest that the incorporation of BST-2 into viral envelopes underlies its broad restrictive activity, whereas its relative exclusion from virions and sites of viral assembly by proteins such as HIV-1 Vpu may provide viral antagonism of restriction.
Zdroje
1. MalimMH
EmermanM
2008 HIV-1 accessory proteins–ensuring viral survival in a hostile environment. Cell Host Microbe 3 388 398
2. KlimkaitT
StrebelK
HogganMD
MartinMA
OrensteinJM
1990 The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release. J Virol 64(2) 621 629
3. VarthakaviV
SmithRM
BourSP
StrebelK
SpearmanP
2003 Viral protein U counteracts a human host cell restriction that inhibits HIV-1 particle production. Proc Natl Acad Sci U S A 100 15154 15159
4. NeilSJ
ZangT
BieniaszPD
2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451 425 430
5. Van DammeN
GoffD
KatsuraC
JorgensonRL
MitchellR
2008 The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3 245 252
6. OhtomoT
SugamataY
OzakiY
OnoK
YoshimuraY
1999 Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells. Biochem Biophys Res Commun 258 583 591
7. BlasiusAL
GiurisatoE
CellaM
SchreiberRD
ShawAS
2006 Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. J Immunol 177 3260 3265
8. KupzigS
KorolchukV
RollasonR
SugdenA
WildeA
2003 Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4 694 709
9. JouvenetN
NeilSJ
ZhadinaM
ZangT
KratovacZ
2009 Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 83 1837 1844
10. SakumaT
NodaT
UrataS
KawaokaY
YasudaJ
2008 Inhibition of Lassa and Marburg virus production by tetherin. J Virol 83 2382 2385
11. Le TortorecA
NeilSJ
2009 Antagonism and intracellular sequestration of human tetherin by the HIV-2 envelope glycoprotein. J Virol Sept 9 Epub.
12. JiaB
Serra-MorenoR
NeidermyerW
RahmbergA
MackeyJ
2009 Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5 e1000429 doi:10.1371/journal.ppat.1000429
13. BarteeE
McCormackA
FruhK
2006 Quantitative membrane proteomics reveals new cellular targets of viral immune modulators. PLoS Pathog 2 e107 doi:10.1371/journal.ppat.0020107
14. KaletskyRL
FrancicaJR
Grawal-GamseC
BatesP
2009 Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A 106 2886 2891
15. NguyenDH
HildrethJEK
2000 Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74 3264 3272
16. PanchalRG
RuthelG
KennyTA
KallstromGH
LaneD
2003 In vivo oligomerization and raft localization of Ebola virus protein VP40 during vesicular budding. Proc Natl Acad Sci U S A 100 15936 15941
17. KawaiS
YoshimuraY
IidaS
KinoshitaY
KoishiharaY
2006 Antitumor activity of humanized monoclonal antibody against HM1.24 antigen in human myeloma xenograft models. Oncol Rep 15 361 367
18. GiepmansBN
DeerinckTJ
SmarrBL
JonesYZ
EllismanMH
2005 Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots. Nat Methods 2 743 749
19. MitchellRS
KatsuraC
SkaskoMA
FitzpatrickK
LauD
2009 Vpu antagonizes BST-2-mediated restriction of HIV-1 release via β-TrCP and endo-lysosomal trafficking. PLoS Pathog 5 e1000450 doi:10.1371/journal.ppat.1000450
20. OrentasRJ
HildrethJE
1993 Association of host cell surface adhesion receptors and other membrane proteins with HIV and SIV. AIDS Res Hum Retroviruses 9 1157 1165
21. EsserMT
GrahamDR
CorenLV
TrubeyCM
Bess JWJr
2001 Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation. J Virol 75 6173 6182
22. NeilSJ
EastmanSW
JouvenetN
BieniaszPD
2006 HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane. PLoS Pathog 2 e39 doi:10.1371/journal.ppat.0020039
23. MiyagiE
AndrewAJ
KaoS
StrebelK
2009 Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion. Proc Natl Acad Sci U S A 106 2868 73
24. GoffinetC
AllespachI
HomannS
TervoHM
HabermannA
2009 HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe 5 285 297
25. AndrewAJ
MiyagiE
KaoS
StrebelK
2009 The formation of cysteine-linked dimers of BST-2/tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to Vpu. Retrovirology 6: 80 Epub
26. SakumaT
SakuraiA
YasudaJ
2009 Dimerization of tetherin is not essential for its antiviral activity against Lassa and Marburg viruses. PLoS ONE 4 e6934 doi:10.1371/journal.pone.0006934
27. Vidal-LalienaM
RomeroX
MarchS
RequenaV
PetrizJ
2005 Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry. Cell Immunol 236 6 16
28. CaoW
BoverL
ChoM
WenX
HanabuchiS
2009 Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 206 1603 14
29. Perez-CaballeroD
ZangT
EbrahimiA
McNattMW
GregoryDA
2009 Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139 499 511
30. AdachiA
GendelmanHE
KoenigS
FolksT
WilleyR
1986 Production of acquired immunodeficiency syndrome-associated retrovirus in human and non-human cells transfected with an infectious molecular clone. J Virol 59 284 291
31. SchubertU
BourS
Ferrer-MontielAV
MontalM
MaldarellF
1996 The two biological activities of human immunodeficiency virus type 1 Vpu protein involve two separable structural domains. J Virol 70 809 819
32. ClavelF
CharneauP
1994 Fusion from without directed by human immunodeficiency virus particles. J Virol 68 1179 1185
33. KremerJR
MastronardeDN
McIntoshJR
1996 Computer visualization of three-dimensional image data using IMOD. J Struct Biol 116 71 76
34. LawrenceA
BouwerJC
PerkinsG
EllismanMH
2006 Transform-based backprojection for volume reconstruction of large format electron microscope tilt series. J Struct Biol 154 144 167
35. DayJR
MartinezLE
SasikR
HitchinDL
DueckME
2006 A computer-based, image-analysis method to quantify HIV-1 infection in a single-cycle infectious center assay. J Virological Methods 137 125 133
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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