Structure of Aichi Virus 1 and Its Empty Particle: Clues to Kobuvirus Genome Release Mechanism.
Aichi virus 1(AiV-1) is a human pathogen from theKobuvirusgenus of thePicornaviridaefamily. Worldwide, 80 to 95% of adults have antibodies against the virus. AiV-1 infections are associated with nausea, gastroenteritis, and fever. Unlike most picornaviruses, kobuvirus capsids are composed of only three types of subunits: VP0, VP1, and VP3. We present here the structure of the AiV-1 virion determined to a resolution of 2.1 Å using X-ray crystallography. The surface loop puff of VP0 and knob of VP3 in AiV-1 are shorter than those in other picornaviruses. Instead, the 42-residue BC loop of VP0 forms the most prominent surface feature of the AiV-1 virion. We determined the structure of AiV-1 empty particle to a resolution of 4.2 Å using cryo-electron microscopy. The empty capsids are expanded relative to the native virus. The N-terminal arms of capsid proteins VP0, which mediate contacts between the pentamers of capsid protein protomers in the native AiV-1 virion, are disordered in the empty capsid. Nevertheless, the empty particles are stable, at leastin vitro, and do not contain pores that might serve as channels for genome release. Therefore, extensive and probably reversible local reorganization of AiV-1 capsid is required for its genome release.IMPORTANCEAichi virus 1 (AiV-1) is a human pathogen that can cause diarrhea, abdominal pain, nausea, vomiting, and fever. AiV-1 is identified in environmental screening studies with higher frequency and greater abundance than other human enteric viruses. Accordingly, 80 to 95% of adults worldwide have suffered from AiV-1 infections. We determined the structure of the AiV-1 virion. Based on the structure, we show that antiviral compounds that were developed against related enteroviruses are unlikely to be effective against AiV-1. The surface of the AiV-1 virion has a unique topology distinct from other related viruses from thePicornaviridaefamily. We also determined that AiV-1 capsids form compact shells even after genome release. Therefore, AiV-1 genome release requires large localized and probably reversible reorganization of the capsid.
Structural Virology, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Charles
C
Sabin
Structural Virology, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Tibor
T
Füzik
Structural Virology, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Karel
K
Škubník
Structural Virology, Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Lenka
L
Pálková
Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden.
A Michael
AM
Lindberg
Structural Virology, Central European Institute of Technology, Masaryk University, Brno, Czech Republic pavel.plevka@ceitec.muni.cz.
Pavel
P
Plevka
Microbiol Immunol. 1995;39(6):433-5
8551977
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2061-5
1549565
Trends Microbiol. 2002 Jul;10(7):324-31
12110211
Nature. 1987 Jun 11-17;327(6122):482-6
3035380
Science. 1987 Jan 9;235(4785):182-91
3026048
Arch Virol. 2006 Jun;151(6):1199-206
16421634
J Infect Dis. 1991 Nov;164(5):954-7
1658159
J Mol Biol. 2002 Jan 25;315(4):663-76
11812138
J Struct Biol. 2003 Jun;142(3):334-47
12781660
J Mol Biol. 2003 Oct 31;333(4):721-45
14568533
Curr Biol. 1994 Sep 1;4(9):784-97
7820548
Nat Protoc. 2007;2(11):2728-33
18007608
Curr Top Microbiol Immunol. 2010;343:43-89
20397067
Nat Struct Biol. 2001 Oct;8(10):874-8
11573093
J Struct Biol. 2012 Dec;180(3):519-30
23000701
Science. 2012 Jun 8;336(6086):1274
22383808
J Virol. 1998 Oct;72(10):8408-12
9733894
PLoS Pathog. 2013 Mar;9(3):e1003240
23555253
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67
22505256
Pathogens. 2015 May 19;4(2):256-68
25996404
Epidemiol Infect. 2010 Aug;138(8):1166-71
19961643
Nature. 1985 Sep 12-18;317(6033):145-53
2993920
Nat Protoc. 2008;3(12):1941-74
19180078
Acta Crystallogr D Biol Crystallogr. 1994 Mar 1;50(Pt 2):178-85
15299456
Science. 1985 Sep 27;229(4720):1358-65
2994218
J Virol. 1990 May;64(5):1934-45
2157861
Nature. 1989 Feb 23;337(6209):709-16
2537470
J Virol. 2004 Mar;78(6):2935-42
14990711
J Virol. 2010 Dec;84(24):12665-74
20881044
Microbiol Rev. 1981 Jun;45(2):287-315
7022155
J Virol. 2010 May;84(9):4426-41
20181687
J Comput Chem. 2004 Oct;25(13):1605-12
15264254
J Clin Microbiol. 2008 Apr;46(4):1252-8
18256215
J Virol. 2001 Mar;75(5):2444-51
11160747
Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9
2025413
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18284-9
19011098
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
17452350
Structure. 1997 Mar 15;5(3):427-41
9083115
J Mol Biol. 2012 Oct 5;422(5):650-8
22743104
J Virol. 2012 Jul;86(13):7207-15
22514349
PLoS Pathog. 2009 Oct;5(10):e1000620
19816570
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):507-11
8093643
Acta Crystallogr D Biol Crystallogr. 1999 Nov;55(Pt 11):1878-84
10531486
J Virol. 2014 Mar;88(6):3114-26
24352461
Nat Struct Mol Biol. 2012 Mar 04;19(4):424-9
22388738
J Virol. 1994 Jun;68(6):3713-23
8189509
J Struct Biol. 2007 Jan;157(1):38-46
16859925
J Virol. 1982 Dec;44(3):900-6
6294338
J Virol. 2011 Oct;85(19):9974-83
21775460
Arch Virol. 2003 Jun;148(6):1225-33
12756627
Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14730-5
10611281
Mol Pathol. 2002 Aug;55(4):214-9
12147709
J Clin Microbiol. 1993 Nov;31(11):2938-43
8263178
PLoS Pathog. 2013;9(4):e1003270
23592991
Nat Methods. 2012 Sep;9(9):853-4
22842542
J Virol. 2014 Feb;88(3):1758-70
24257617
Virology. 1991 Feb;180(2):781-7
1846498
J Virol. 2011 Jan;85(2):776-83
20980499
PLoS Pathog. 2012 Jan;8(1):e1002473
22241997
Nat Struct Biol. 1999 Aug;6(8):765-74
10426956
Virology. 1984 Jun;135(2):546-50
6204448
Science. 1986 Sep 19;233(4770):1286-93
3018924
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
15572765
Nature. 2015 Jan 1;517(7532):85-8
25327248
J Virol. 2015 Nov 18;90(3):1377-86
26581987
J Virol. 2016 Aug 12;90(17):7628-39
27279624
J Virol. 1999 Jan;73(1):427-35
9847348
Acta Crystallogr F Struct Biol Commun. 2016 Mar;72 (Pt 3):188-97
26919522
J Virol. 2000 Feb;74(3):1342-54
10627545
J Clin Microbiol. 2008 Apr;46(4):1349-55
18287312
Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):473-89
15299834
Nat Commun. 2015 Oct 08;6:8316
26446437
Proteins. 1992 Oct;14(2):309-23
1409577
Nat Commun. 2013;4:1929
23728514
Mol Cell. 2002 Aug;10(2):317-26
12191477
J Virol. 1991 Nov;65(11):6015-23
1681115
Microbiol Mol Biol Rev. 2014 Sep;78(3):418-37
25184560