Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission
The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.
Vyšlo v časopise:
Tetherin Restricts Productive HIV-1 Cell-to-Cell Transmission. PLoS Pathog 6(6): e32767. doi:10.1371/journal.ppat.1000955
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1000955
Souhrn
The IFN-inducible antiviral protein tetherin (or BST-2/CD317/HM1.24) impairs release of mature HIV-1 particles from infected cells. HIV-1 Vpu antagonizes the effect of tetherin. The fate of virions trapped at the cell surface remains poorly understood. Here, we asked whether tetherin impairs HIV cell-to-cell transmission, a major means of viral spread. Tetherin-positive or -negative cells, infected with wild-type or ΔVpu HIV, were used as donor cells and cocultivated with target lymphocytes. We show that tetherin inhibits productive cell-to-cell transmission of ΔVpu to targets and impairs that of WT HIV. Tetherin accumulates with Gag at the contact zone between infected and target cells, but does not prevent the formation of virological synapses. In the presence of tetherin, viruses are then mostly transferred to targets as abnormally large patches. These viral aggregates do not efficiently promote infection after transfer, because they accumulate at the surface of target cells and are impaired in their fusion capacities. Tetherin, by imprinting virions in donor cells, is the first example of a surface restriction factor limiting viral cell-to-cell spread.
Zdroje
1. SattentauQ
2008 Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 6 815 826
2. ChenP
HubnerW
SpinelliMA
ChenBK
2007 Predominant mode of human immunodeficiency virus transfer between T cells is mediated by sustained Env-dependent neutralization-resistant virological synapses. J Virol 81 12582 12595
3. RudnickaD
FeldmannJ
PorrotF
WietgrefeS
GuadagniniS
2009 Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses. J Virol 83 6234 6246
4. ShererNM
LehmannMJ
Jimenez-SotoLF
HorensavitzC
PypaertM
2007 Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission. Nat Cell Biol 9 310 315
5. SowinskiS
JollyC
BerninghausenO
PurbhooMA
ChauveauA
2008 Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol 10 211 219
6. Pais-CorreiaAM
SachseM
GuadagniniS
RobbiatiV
LasserreR
2009 Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat Med
7. RuggieroE
BonaR
MuratoriC
FedericoM
2008 Virological consequences of early events following cell-cell contact between human immunodeficiency virus type 1-infected and uninfected CD4+ cells. J Virol 82 7773 7789
8. HubnerW
McNerneyGP
ChenP
DaleBM
GordonRE
2009 Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science 323 1743 1747
9. BoschB
GrigorovB
SenserrichJ
ClotetB
DarlixJL
2008 A clathrin-dynamin-dependent endocytic pathway for the uptake of HIV-1 by direct T cell-T cell transmission. Antiviral Res 80 185 193
10. VendrameD
SourisseauM
PerrinV
SchwartzO
MammanoF
2009 Partial Inhibition of HIV Replication by Type-I Interferons: Impact of Cell-to-Cell Viral Transfer. J Virol
11. NeilSJ
ZangT
BieniaszPD
2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451 425 430
12. 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
13. JouvenetN
NeilSJ
ZhadinaM
ZangT
KratovacZ
2009 Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 83 1837 1844
14. SakumaT
NodaT
UrataS
KawaokaY
YasudaJ
2009 Inhibition of Lassa and Marburg virus production by tetherin. J Virol 83 2382 2385
15. GroomHC
YapMW
GalaoRP
NeilSJ
BishopKN
2010 Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors. Proc Natl Acad Sci U S A 107 5166 5171
16. ArnaudF
BlackS
MurphyL
GriffithsD
NeilSJ
2010 Interplay Between Ovine Bone Marrow Stromal Cell Antigen 2 (BST2)/Tetherin and Endogenous Retroviruses. J Virol
17. MattiuzzoG
IvolS
TakeuchiY
2010 Regulation of porcine endogenous retrovirus release by porcine and human tetherins. J Virol 84 2618 2622
18. GuptaRK
HueS
SchallerT
VerschoorE
PillayD
2009 Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathog 5 e1000443
19. DouglasJL
ViswanathanK
McCarrollMN
GustinJK
FruhK
2009 Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J Virol 83 7931 7947
20. MitchellRS
KatsuraC
SkaskoMA
FitzpatrickK
LauD
2009 Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog 5 e1000450
21. 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
22. MangeatB
Gers-HuberG
LehmannM
ZuffereyM
LubanJ
2009 HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog 5 e1000574
23. IwabuY
FujitaH
KinomotoM
KanekoK
IshizakaY
2009 HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem
24. GuptaRK
MlcochovaP
Pelchen-MatthewsA
PetitSJ
MattiuzzoG
2009 Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A
25. 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
26. LimES
EmermanM
2009 Simian immunodeficiency virus SIVagm from African green monkeys does not antagonize endogenous levels of african green monkey tetherin/BST-2. J Virol 83 11673 11681
27. ZhangF
WilsonSJ
LandfordWC
VirgenB
GregoryD
2009 Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6 54 67
28. SauterD
SchindlerM
SpechtA
LandfordWN
MunchJ
2009 Tetherin-Driven Adaptation of Vpu and Nef Function and the Evolution of Pandemic and Nonpandemic HIV-1 Strains. Cell Host Microbe 6 409 421
29. McNattMW
ZangT
HatziioannouT
BartlettM
FofanaIB
2009 Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants. PLoS Pathog 5 e1000300
30. Perez-CaballeroD
ZangT
EbrahimiA
McNattMW
GregoryDA
2009 Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139 499 511
31. FitzpatrickK
SkaskoM
DeerinckTJ
CrumJ
EllismanMH
2010 Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles. PLoS Pathog 6 e1000701
32. RollasonR
KorolchukV
HamiltonC
SchuP
BantingG
2007 Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J Cell Sci 120 3850 3858
33. RollasonR
KorolchukV
HamiltonC
JepsonM
BantingG
2009 A CD317/tetherin-RICH2 complex plays a critical role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. J Cell Biol 184 721 736
34. 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
35. NguyenDH
HildrethJE
2000 Evidence for budding of human immunodeficiency virus type 1 selectively from glycolipid-enriched membrane lipid rafts. J Virol 74 3264 3272
36. OnoA
FreedEO
2001 Plasma membrane rafts play a critical role in HIV-1 assembly and release. Proc Natl Acad Sci U S A 98 13925 13930
37. MiyakawaK
RyoA
MurakamiT
OhbaK
YamaokaS
2009 BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS Pathog 5 e1000700
38. 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
39. SourisseauM
Sol-FoulonN
PorrotF
BlanchetF
SchwartzO
2007 Inefficient human immunodeficiency virus replication in mobile lymphocytes. J Virol 81 1000 1012
40. CavroisM
De NoronhaC
GreeneWC
2002 A sensitive and specific enzyme-based assay detecting HIV-1 virion fusion in primary T lymphocytes. Nat Biotechnol 20 1151 1154
41. BergeronL
SullivanN
SodroskiJ
1992 Target cell-specific determinants of membrane fusion within the Human Immunodeficiency virus type 1 gp120 third variable region and gp41 amino terminus. J Virol 66 2389 2397
42. NobileC
PetitC
MorisA
SkrabalK
AbastadoJP
2005 Covert human immunodeficiency virus replication in dendritic cells and in DC-SIGN-expressing cells promotes long-term transmission to lymphocytes. J Virol 79 5386 5399
43. PuigdomenechI
MassanellaM
CabreraC
ClotetB
BlancoJ
2009 On the steps of cell-to-cell HIV transmission between CD4 T cells. Retrovirology 6 89
44. MiyauchiK
KimY
LatinovicO
MorozovV
MelikyanGB
2009 HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell 137 433 444
45. GummuluruS
KinseyCM
EmermanM
2000 An in vitro rapid-turnover assay for human immunodeficiency virus type 1 replication selects for cell-to-cell spread of virus. J Virol 74 10882 10891
46. SchubertU
ClouseKA
StrebelK
1995 Augmentation of virus secretion by the human immunodeficiency virus type 1 Vpu protein is cell type independent and occurs in cultured human primary macrophages and lymphocytes. J Virol 69 7699 7711
47. MullerB
DaeckeJ
FacklerOT
DittmarMT
ZentgrafH
2004 Construction and characterization of a fluorescently labeled infectious human immunodeficiency virus type 1 derivative. J Virol 78 10803 10813
48. Avettand-FenoelV
PrazuckT
HocquelouxL
MelardA
MichauC
2008 HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors. Aids 22 1880 1882
49. Sol-FoulonN
SourisseauM
PorrotF
ThoulouzeMI
TrouilletC
2007 ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation. Embo J 26 516 526
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2010 Číslo 6
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Requirement of NOX2 and Reactive Oxygen Species for Efficient RIG-I-Mediated Antiviral Response through Regulation of MAVS Expression
- Formation of Complexes at Plasmodesmata for Potyvirus Intercellular Movement Is Mediated by the Viral Protein P3N-PIPO
- Insight into the Mechanisms of Adenovirus Capsid Disassembly from Studies of Defensin Neutralization
- Two Novel Point Mutations in Clinical Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection