Novel Escape Mutants Suggest an Extensive TRIM5α Binding Site
Spanning the Entire Outer Surface of the Murine Leukemia Virus Capsid
Protein
After entry into target cells, retroviruses encounter the host restriction
factors such as Fv1 and TRIM5α. While it is clear that these factors target
retrovirus capsid proteins (CA), recognition remains poorly defined in the
absence of structural information. To better understand the binding interaction
between TRIM5α and CA, we selected a panel of novel N-tropic murine
leukaemia virus (N-MLV) escape mutants by a serial passage of replication
competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using
a small percentage of unrestricted cells to allow multiple rounds of virus
replication. The newly identified mutations, many of which involve changes in
charge, are distributed over the outer ‘top’ surface of N-MLV CA,
including the N-terminal β-hairpin, and map up to 29 Ao apart.
Biological characterisation with a number of restriction factors revealed that
only one of the new mutations affects restriction by human TRIM5α,
indicating significant differences in the binding interaction between N-MLV and
the two TRIM5αs, whereas three of the mutations result in dual sensitivity
to Fv1n and Fv1b. Structural studies of two mutants show
that no major changes in the overall CA conformation are associated with escape
from restriction. We conclude that interactions involving much, if not all, of
the surface of CA are vital for TRIM5α binding.
Vyšlo v časopise:
Novel Escape Mutants Suggest an Extensive TRIM5α Binding Site
Spanning the Entire Outer Surface of the Murine Leukemia Virus Capsid
Protein. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1002011
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002011
Souhrn
After entry into target cells, retroviruses encounter the host restriction
factors such as Fv1 and TRIM5α. While it is clear that these factors target
retrovirus capsid proteins (CA), recognition remains poorly defined in the
absence of structural information. To better understand the binding interaction
between TRIM5α and CA, we selected a panel of novel N-tropic murine
leukaemia virus (N-MLV) escape mutants by a serial passage of replication
competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using
a small percentage of unrestricted cells to allow multiple rounds of virus
replication. The newly identified mutations, many of which involve changes in
charge, are distributed over the outer ‘top’ surface of N-MLV CA,
including the N-terminal β-hairpin, and map up to 29 Ao apart.
Biological characterisation with a number of restriction factors revealed that
only one of the new mutations affects restriction by human TRIM5α,
indicating significant differences in the binding interaction between N-MLV and
the two TRIM5αs, whereas three of the mutations result in dual sensitivity
to Fv1n and Fv1b. Structural studies of two mutants show
that no major changes in the overall CA conformation are associated with escape
from restriction. We conclude that interactions involving much, if not all, of
the surface of CA are vital for TRIM5α binding.
Zdroje
1. LillyF
1970
Fv-2: Identification and location of a second gene governing the
spleen focus response to Friend leukemia virus in mice.
J Natl Cancer Inst
45
163
169
2. PincusTHartleyJWRoweWP
1971
A major genetic locus affecting resistance to infection with
murine leukemia viruses. I. Tissue culture studies of naturally occurring
viruses.
J Exp Med
133
1219
1233
3. PincusTRoweWPLillyF
1971
A major genetic locus affecting resistance to infection with
murine leukemia viruses. II. Apparent identity to a major locus described
for resistance to Friend murine leukemia virus.
J Exp Med
133
1234
1241
4. HofmannWSchubertDLaBonteJMunsonLGibsonS
1999
Species-specific, postentry barriers to primate immunodeficiency
virus infection.
J Virol
73
10020
10028
5. StremlauMOwensCMPerronMJKiesslingMAutisslerP
2004
The cytoplasmic body component TRIM5α restricts HIV-1
infection in Old World monkeys.
Nature
427
848
853
6. HatziioannouTPerez-CaballeroDYangACowanSBieniaszPD
2004
Retrovirus resistance factors Ref1 and Lv1 are species-specific
variants of TRIM5α.
Proc Natl Acad Sci U S A
101
10774
10779
7. KeckesovaZYlinenLMJTowersGJ
2004
The human and African green monkey TRIM5α genes encode Ref1
and Lv1 retroviral restriction factor activities.
Proc Natl Acad Sci U S A
101
10780
10785
8. YapMWNisoleSLynchCStoyeJP
2004
Trim5α protein restricts both HIV-1 and murine leukemia
virus.
Proc Natl Acad Sci U S A
101
10786
10791
9. ReymondAMeroniGFantozziAMerlaGCairoS
2001
The tripartite motif family identifies cell
compartments.
EMBO J
20
2140
2151
10. NisoleSStoyeJPSaïbA
2005
Trim family proteins: retroviral restriction and antiviral
defence.
Nat Rev Microbiol
3
799
808
11. SardielloMCairoSFontanellaBBallabioAMeroniG
2008
Genomic analysis of the TRIM family reveals two groups of genes
with distinct evolutionary properties.
BMC Evol Biol
8
225
12. ShortKMCoxTC
2006
Sub-classification of the RBCC/TRIM superfamily reveals a novel
motif necessary for microtubule binding.
J Biol Chem
281
8970
8980
13. Perez-CaballeroDHatziioannouTYangACowanSBieniaszPD
2005
Human tripartite motif 5α domains responsible for retrovirus
restriction activity and specificity.
J Virol
79
8969
8978
14. SawyerSLWuLIEmermanMMalikHS
2005
Positive selection of primate TRIM5α identifies a critical
species-specific retroviral restriction domain.
Proc Natl Acad Sci U S A
102
In Press
15. SongBGoldBO'hUiginCJavanbakhtMLiX
2005
The B30.2(SPRY) domain of retroviral restriction factor
TRIM5α exhibits lineage-specific length and sequence variation in
primates.
J Virol
79
6111
6121
16. YapMWNisoleSStoyeJP
2005
A single amino acid change in the SPRY domain of human Trim5α
leads to HIV-1 restriction.
Curr Biol
15
73
78
17. BooneLRMyerFEYangDMOuC-YKohCK
1983
Reversal of Fv-1 host range by in vitro
restriction endonuclease fragment exchange between molecular clones of
N-tropic and B-tropic murine leukemia virus genomes.
J Virol
48
110
119
18. DesGroseillersLJolicoeurP
1983
Physical mapping of the Fv-1 tropism host range determinant of
BALB/c murine leukemia viruses.
J Virol
48
685
696
19. TowersGBockMMartinSTakeuchiYStoyeJP
2000
A conserved mechanism of retrovirus restriction in
mammals.
Proc Natl Acad Sci, USA
97
12295
12299
20. WuXAndersonJLCampbellEMJosephAMHopeTJ
2006
Proteasome inhibitors uncouple rhesus TRIM5α restriction of
HIV-1 reverse transcription and infection.
Proc Natl Acad Sci U S A
103
21. JolicoeurPBaltimoreD
1976
Effect of Fv-1 gene product on proviral DNA formation and
integration in cells infected with murine leukemia viruses.
Proc Natl Acad Sci, USA
73
2236
2240
22. PryciakPMVarmusHE
1992
Fv-1 restriction and its effects on murine
leukemia virus integration in vivo and in vitro.
J Virol
66
5959
5966
23. DiehlWEStansellEKaiserSMEmermanMHunterE
2008
Identification of Post-entry Restrictions to Mason-Pfizer Monkey
Virus Infection in New World Monkey Cells.
J Virol
82
11140
11151
24. OhkuraSYapMWSheldonTStoyeJP
2006
All three variable regions of the TRIM5α B30.2 domain can
contribute to the specificity of retrovirus restriction.
J Virol
80
8554
8565
25. YapMWLindemannDStankeNRehJWestphalD
2008
Restriction of foamy viruses by primate
Trim5alpha.
J Virol
82
5429
5439
26. Diaz-GrifferoFQinX-RHayashiFKigawaTFinziA
2009
A B-box 2 surface patch important for TRIM5α
self-association, capsid binding avidity and retrovirus
restriction.
J Virol
83
10737
10751
27. MortuzaGBDoddingMPGoldstoneDCHaireLFStoyeJP
2008
Structure of B-MLV capsid amino-terminal domain reveals key
features of viral tropism, gag assembly and core formation.
J Mol Biol
376
1493
1508
28. YapMWMortuzaGBTaylorIAStoyeJP
2007
The design of artificial retroviral restriction
factors.
Virology
365
302
314
29. FallerDVHopkinsN
1978
T1 oligonucleotide maps of N-, B-, and B->NB-tropic
murine leukemia viruses derived from BALB/c.
J Virol
26
143
152
30. StevensABockMEllisSLeTissierPBishopKN
2004
Retroviral capsid determinants of Fv1 NB- and
NR-tropism.
J Virol In Press
31. KozakCAChakrabortiA
1996
Single amino acid changes in the murine leukemia virus capsid
protein gene define the target for Fv1
resistance.
Virology
225
300
306
32. MortuzaGBHaireLFStevensASmerdonSJStoyeJP
2004
High-resolution structure of a retroviral capsid hexameric
amino-terminal domain.
Nature
431
481
485
33. KootstraNAMünkCTonnuNLandauNRVermaIM
2003
Abrogation of postentry restriction of HIV-1-based lentiviral
vector transduction in simian cells.
Proc Natl Acad Sci, USA
100
1298
1303
34. YlinenLMJKeckesovaZWilsonSJRanasingheSTowersGJ
2005
Differential restriction of human immunodeficiency virus type 2
and simian immunodeficiency virus SIVmac by TRIM5α
alleles.
J Virol
79
11580
11587
35. KuroishiABozekKShiodaTNakayamaEE
2010
A single amino acid substitution of the human immunodeficiency
virus type 1 capsid protein affects viral sensitivity to TRIM5
alpha.
Retrovirology
7
58
36. KonoKSongHYokoyamaMSatoHShiodaT
2010
Multiple sites in the N-terminal half of simian immunodeficiency
virus capsid protein contribute to evasion from rhesus monkey
TRIM5alpha-mediated restriction.
Retrovirology
7
72
37. HerrW
1984
Nucleotide sequence of AKV murine leukemia virus.
J Virol
49
471
478
38. StremlauMPerronMLeeMLiYSongB
2006
Specific recognition and accelerated uncoating of retroviral
capsids by the TRIM5α restriction factor.
Proc Natl Acad Sci U S A
103
5514
5519
39. GoldstoneDCYapMWRobertsonLEHaireLFTaylorWR
2010
Structural and functional analysis of prehistoric lentiviruses
uncovers an ancient molecular interface.
Cell Host Microbe
8
248
259
40. JamesLCKeebleAHKhanZRhodesDATrowsdaleJ
2007
Structural basis for PRYSPRY-mediated tripartite motif (TRIM)
protein function.
Proc Natl Acad Sci U S A
104
6200
6205
41. ParkEYKwonOBJeongBCYiJSLeeCS
2010
Crystal structure of PRY-SPRY domain of human
TRIM72.
Proteins
78
790
795
42. MortuzaGBGoldstoneDCPashleyCHaireLFPalmariniM
2009
Structure of the capsid amino-terminal domain from the
betaretrovirus, Jaagsiekte sheep retrovirus.
J Mol Biol
386
1179
1192
43. PachecoBFinziAStremlauMSodroskiJ
2010
Adaptation of HIV-1 to cells expressing rhesus monkey
TRIM5α.
Virology
408
204
212
44. SongHNakayamaEEYokoyamaMSatoHLevyJA
2007
A single amino acid of the human immunodeficiency virus Type 2
Capsid affects its replication in the presence of cynomolgus monkey and
human TRIM5αs.
J Virology
81
7280
7285
45. GambleTRVajdosFFYooSWorthylakeDKHouseweartM
1996
Crystal structure of human cyclophilin A bound to the
amino-terminal domain of HIV-1 capsid.
Cell
87
1285
1294
46. MaillardPVEccoGOrtizMTronoD
2010
The specificity of TRIM5α-mediated restriction is influenced
by its coiled-coil domain.
J Virol
84
5790
5801
47. NewmanRMHallLConnoleMChenGLSatoS
2006
Balancing selection and the evolution of functional polymorphism
in Old World monkey TRIM5alpha.
Proc Natl Acad Sci U S A
103
19134
19139
48. BockMBishopKNTowersGStoyeJP
2000
Use of a transient assay for studying the genetic determinants of
Fv1 restriction.
J Virol
74
7422
7430
49. OtwinowskiZMinorW
1997
Processing of X-ray diffraction data collected in oscillation
mode.
Meth Enzymol
276
307
326
50. McCoyAJGrosse-KunstleveRWAdamsPDWinnMDStoroniLC
2007
Phaser crystallographic software.
J Appl Crystallogr
40
658
674
51. ZwartPHAfoninePVGrosse-KunstleveRWHungLWIoergerTR
2008
Automated structure solution with the PHENIX
suite.
Methods Mol Biol
426
419
435
52. EmsleyPCowtanK
2004
Coot: model-building tools for molecular
graphics.
Acta Crystallogr D Biol Crystallogr
60
2126
2132
53. PainterJMerrittEA
2006
Optimal description of a protein structure in terms of multiple
groups undergoing TLS motion.
Acta Crystallogr D Biol Crystallogr
62
439
450
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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