#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#