#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure


The initial step in target cell infection by human, and the closely related simian immunodeficiency viruses (HIV and SIV, respectively) occurs with the binding of trimeric envelope glycoproteins (Env), composed of heterodimers of the viral transmembrane glycoprotein (gp41) and surface glycoprotein (gp120) to target T-cells. Knowledge of the molecular structure of trimeric Env on intact viruses is important both for understanding the molecular mechanisms underlying virus-cell interactions and for the design of effective immunogen-based vaccines to combat HIV/AIDS. Previous analyses of intact HIV-1 BaL virions have already resulted in structures of trimeric Env in unliganded and CD4-liganded states at ∼20 Å resolution. Here, we show that the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are closely comparable to that previously determined for HIV-1 BaL, with the V1 and V2 variable loops located at the apex of the spike, close to the contact zone between virus and cell. The location of the V1/V2 loops in trimeric Env was definitively confirmed by structural analysis of HIV-1 R3A virions engineered to express Env with deletion of these loops. Strikingly, in SIV CP-MAC, a CD4-independent strain, trimeric Env is in a constitutively “open” conformation with gp120 trimers splayed out in a conformation similar to that seen for HIV-1 BaL Env when it is complexed with sCD4 and the CD4i antibody 17b. Our findings suggest a structural explanation for the molecular mechanism of CD4-independent viral entry and further establish that cryo-electron tomography can be used to discover distinct, functionally relevant quaternary structures of Env displayed on intact viruses.


Vyšlo v časopise: Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure. PLoS Pathog 6(12): e32767. doi:10.1371/journal.ppat.1001249
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1001249

Souhrn

The initial step in target cell infection by human, and the closely related simian immunodeficiency viruses (HIV and SIV, respectively) occurs with the binding of trimeric envelope glycoproteins (Env), composed of heterodimers of the viral transmembrane glycoprotein (gp41) and surface glycoprotein (gp120) to target T-cells. Knowledge of the molecular structure of trimeric Env on intact viruses is important both for understanding the molecular mechanisms underlying virus-cell interactions and for the design of effective immunogen-based vaccines to combat HIV/AIDS. Previous analyses of intact HIV-1 BaL virions have already resulted in structures of trimeric Env in unliganded and CD4-liganded states at ∼20 Å resolution. Here, we show that the molecular architectures of trimeric Env from SIVmneE11S, SIVmac239 and HIV-1 R3A strains are closely comparable to that previously determined for HIV-1 BaL, with the V1 and V2 variable loops located at the apex of the spike, close to the contact zone between virus and cell. The location of the V1/V2 loops in trimeric Env was definitively confirmed by structural analysis of HIV-1 R3A virions engineered to express Env with deletion of these loops. Strikingly, in SIV CP-MAC, a CD4-independent strain, trimeric Env is in a constitutively “open” conformation with gp120 trimers splayed out in a conformation similar to that seen for HIV-1 BaL Env when it is complexed with sCD4 and the CD4i antibody 17b. Our findings suggest a structural explanation for the molecular mechanism of CD4-independent viral entry and further establish that cryo-electron tomography can be used to discover distinct, functionally relevant quaternary structures of Env displayed on intact viruses.


Zdroje

1. WyattR

SodroskiJ

1998 The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280 1884 1888

2. DalgleishAG

BeverleyPC

ClaphamPR

CrawfordDH

GreavesMF

1984 The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312 763 767

3. BurtonDR

DesrosiersRC

DomsRW

KoffWC

KwongPD

2004 HIV vaccine design and the neutralizing antibody problem. Nat Immunol 5 233 236

4. SatoS

JohnsonW

2007 Antibody-mediated neutralization and Simian immunodeficiency virus models of HIV/AIDS. Current HIV Research 5 594 607

5. ChenB

VoganEM

GongH

SkehelJJ

WileyDC

2005 Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433 834 841

6. HuangCC

TangM

ZhangMY

MajeedS

MontabanaE

2005 Structure of a V3-containing HIV-1 gp120 core. Science 310 1025 1028

7. KwongPD

WyattR

RobinsonJ

SweetRW

SodroskiJ

1998 Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393 648 659

8. ZhouT

XuL

DeyB

HessellAJ

Van RykD

2007 Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445 732 737

9. BartesaghiA

SubramaniamS

2009 Membrane protein structure determination using cryo-electron tomography and 3D image averaging. Curr Opin Struct Biol 19 402 407

10. BartesaghiA

SprechmannP

LiuJ

RandallG

SapiroG

2008 Classification and 3D averaging with missing wedge correction in biological electron tomography. J Struct Biol 162 436 450

11. ForsterF

PruggnallerS

SeybertA

FrangakisAS

2008 Classification of cryo-electron sub-tomograms using constrained correlation. J Struct Biol 161 276 286

12. WinklerH

2007 3D reconstruction and processing of volumetric data in cryo-electron tomography. J Struct Biol 157 126 137

13. ZhuP

LiuJ

BessJJr

ChertovaE

LifsonJD

2006 Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441 847 852

14. ZanettiG

BriggsJAG

GrunewaldK

SattentauQJ

FullerSD

2006 Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathogens 2 e83

15. LiuJ

BartesaghiA

BorgniaMJ

SapiroG

SubramaniamS

2008 Molecular architecture of native HIV-1 gp120 trimers. Nature 455 109 113

16. ZhuP

WinklerH

ChertovaE

TaylorKA

RouxKH

2008 Cryoelectron tomography of HIV-1 envelope spikes: Further evidence for tripod-like legs. PLoS Pathogens 4 e1000203

17. LaaksoMM

LeeFH

HaggartyB

AgrawalC

NolanKM

2007 V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies. PLoS Pathog 3 e117

18. EdingerAL

AhujaM

SungT

BaxterKC

HaggartyB

2000 Characterization and epitope mapping of neutralizing monoclonal antibodies produced by immunization with oligomeric simian immunodeficiency virus envelope protein. J Virol 74 7922 7935

19. EndresMJ

ClaphamPR

MarshM

AhujaM

TurnerJD

1996 CD4-independent infection by HIV-2 is mediated by fusin/CXCR4. Cell 87 745 756

20. EdingerAL

BlanpainC

KunstmanKJ

WolinskySM

ParmentierM

1999 Functional dissection of CCR5 coreceptor function through the use of CD4-independent simian immunodeficiency virus strains. J Virol 73 4062 4073

21. BonaviaA

BullockBT

GisselmanKM

MarguliesBJ

ClementsJE

2005 A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using CCR5 in a CD4-independent pathway. Virology 341 12 23

22. ThaliM

MooreJP

FurmanC

CharlesM

HoDD

1993 Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J Virol 67 3978 3988

23. SubramaniamS

2006 The SIV surface spike imaged by electron tomography: one leg or three? PLoS Pathog 2 e91

24. HoffmanTL

LaBrancheCC

ZhangW

CanzianiG

RobinsonJ

1999 Stable exposure of the coreceptor-binding site in a CD4-independent HIV-1 envelope protein. Proc Natl Acad Sci U S A 96 6359 6364

25. KolchinskyP

KiprilovE

SodroskiJ

2001 Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants. J Virol 75 2041 2050

26. PufferBA

AltamuraLA

PiersonTC

DomsRW

2004 Determinants within gp120 and gp41 contribute to CD4 independence of SIV Envs. Virology 327 16 25

27. EdingerAL

MankowskiJL

DoranzBJ

MarguliesBJ

LeeB

1997 CD4-independent, CCR5-dependent infection of brain capillary endothelial cells by a neurovirulent simian immunodeficiency virus strain. Proc Natl Acad Sci U S A 94 14742 14747

28. LabrancheCC

SauterMM

HaggartyBS

VancePJ

RomanoJ

1994 Biological, molecular, and structural analysis of a cytopathic variant from a molecularly cloned simian immunodeficiency virus. Journal of Virology 68 5509 5522

29. RossioJL

EsserMT

SuryanarayanaK

SchneiderDK

BessJWJr

1998 Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins. J Virol 72 7992 8001

30. MeansRE

MatthewsT

HoxieJA

MalimMH

KodamaT

2001 Ability of the V3 loop of simian immunodeficiency virus to serve as a target for antibody-mediated neutralization: correlation of neutralization sensitivity, growth in macrophages, and decreased dependence on CD4. J Virol 75 3903 3915

31. KremerJR

MastronardeDN

McIntoshJR

1996 Computer visualization of three-dimensional image data using IMOD. J Struct Biol 116 71 76

32. BartesaghiA

SapiroG

SubramaniamS

2005 An energy-based three-dimensional segmentation approach for the quantitative interpretation of electron tomograms. IEEE Trans Image Process 14 1314 1323

33. PettersenE

GoddardT

HuangC

CouchG

GreenblattECM

ThomasEFerrin

2004 UCSF Chimera - A visualization system for exploratory research and analysis. Journal of Computational Chemistry 25 1605 1612

34. RizzutoCD

WyattR

Hernandez-RamosN

SunY

KwongPD

1998 A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280 1949 1953

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 12
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#