title: To build a virus on a nucleic acid substrate.
abstract: Many viruses package their genomes concomitant with assembly. Here, we show that this reaction can be described by three coefficients: association of capsid protein (CP) to nucleic acid (NA), KNA; CP-CP interaction, ω; and α, proportional to the work required to package NA. The value of α can vary as NA is packaged. A phase diagram of average lnα versus lnω identifies conditions where assembly is likely to fail or succeed. NA morphology can favor (lnα > 0) or impede (lnα < 0) assembly. As lnω becomes larger, capsids become more stable and assembly becomes more cooperative. Where (lnα + lnω) < 0, the CP is unable to contain the NA, so that assembly results in aberrant particles. This phase diagram is consistent with quantitative studies of cowpea chlorotic mottle virus, hepatitis B virus, and simian virus 40 assembling on ssRNA and dsDNA substrates. Thus, the formalism we develop is suitable for describing and predicting behavior of experimental studies of CP assembly on NA.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, Indiana, USA. azlotnic@indiana.edu
authors.forename: Adam
authors.initials: A
authors.lastname: Zlotnick
authors.forename: J Zachary
authors.initials: JZ
authors.lastname: Porterfield
authors.forename: Joseph Che-Yen
authors.initials: JC
authors.lastname: Wang
mesh_terms: D036022:Capsid Proteins / Q000378:metabolism; D042003:DNA Packaging; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism; D014780:Viruses / Q000235:genetics* / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D004279:DNA, Viral; D012367:RNA, Viral
references.citation: J Mol Biol. 1997 Nov 14;273(5):1048-60
references.pmid: 9367790
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2010 May;81(5 Pt 1):051919
references.pmid: 20866273
references.citation: PLoS Pathog. 2012 Sep;8(9):e1002919
references.pmid: 23028319
references.citation: Cell. 1999 May 14;97(4):481-90
references.pmid: 10338212
references.citation: J Virol. 2001 Aug;75(16):7321-9
references.pmid: 11462004
references.citation: J Chem Phys. 2009 Oct 21;131(15):155101
references.pmid: 20568884
references.citation: Biophys J. 2010 Jul 21;99(2):619-28
references.pmid: 20643082
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3173-8
references.pmid: 12629206
references.citation: Hum Gene Ther. 2003 Jan 20;14(2):167-77
references.pmid: 12614568
references.citation: J Mol Biol. 1994 Aug 5;241(1):59-67
references.pmid: 8051707
references.citation: Nature. 1993 Jan 14;361(6408):179-82
references.pmid: 8421525
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16153-8
references.pmid: 18845685
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2007 May;75(5 Pt 1):051901
references.pmid: 17677092
references.citation: J Mol Biol. 1974 Jun 25;86(2):469-89
references.pmid: 4416620
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15769-74
references.pmid: 23019360
references.citation: J Chem Phys. 2009 Mar 21;130(11):114902
references.pmid: 19317561
references.citation: Biophys J. 2008 Feb 15;94(4):1428-36
references.pmid: 17981893
references.citation: Methods Enzymol. 2009;455:395-417
references.pmid: 19289214
references.citation: ACS Chem Biol. 2010 Dec 17;5(12):1125-36
references.pmid: 20845949
references.citation: J Mol Biol. 2008 Aug 1;381(1):229-37
references.pmid: 18585738
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10477-82
references.pmid: 12928495
references.citation: Biophys J. 2011 Jul 6;101(1):167-75
references.pmid: 21723827
references.citation: Biochemistry. 2002 Oct 1;41(39):11525-31
references.pmid: 12269796
references.citation: Biopolymers. 2009 Jul;91(7):530-8
references.pmid: 19226622
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1354-9
references.pmid: 17227841
references.citation: Biophys J. 2003 Mar;84(3):1616-27
references.pmid: 12609865
references.citation: J Virol. 2010 Jul;84(14):7174-84
references.pmid: 20427522
references.citation: J Mol Biol. 2004 Jan 9;335(2):455-64
references.pmid: 14672655
references.citation: RNA. 2012 Feb;18(2):284-99
references.pmid: 22190747
references.citation: J Phys Condens Matter. 2010 Mar 17;22(10):104115
references.pmid: 21389449
references.citation: Biophys J. 2008 Jul;95(2):497-502
references.pmid: 18487310
references.citation: Virology. 2010 Feb 5;397(1):199-204
references.pmid: 19942248
references.citation: Virology. 2012 Aug 15;430(1):20-9
references.pmid: 22595445
references.citation: Biophys J. 2009 Jan;96(1):9-20
references.pmid: 18931258
references.citation: Biochemistry. 1986 Mar 25;25(6):1226-40
references.pmid: 3486003
references.citation: Virus Res. 2008 Jun;134(1-2):235-49
references.pmid: 18339439
references.citation: Nano Lett. 2006 Sep;6(9):1993-9
references.pmid: 16968014
references.citation: Virology. 1991 Jul;183(1):405-9
references.pmid: 2053290
references.citation: Nat Struct Biol. 2001 Jan;8(1):77-83
references.pmid: 11135676
references.citation: Biomacromolecules. 2010 Feb 8;11(2):439-42
references.pmid: 20136150
references.citation: J Gen Virol. 2003 Jul;84(Pt 7):1899-1905
references.pmid: 12810885
references.citation: Annu Rev Microbiol. 2006;60:51-67
references.pmid: 16704342
references.citation: Phys Biol. 2010 Dec 09;7(4):045003
references.pmid: 21149971
references.citation: J Virol. 1999 Jul;73(7):5731-40
references.pmid: 10364324
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2008 May;77(5 Pt 1):051904
references.pmid: 18643099
references.citation: Science. 1989 Jul 14;245(4914):154-9
references.pmid: 2749253
references.citation: Protein Sci. 2005 Jun;14(6):1518-25
references.pmid: 15930000
references.citation: J Biol Chem. 1989 Jan 15;264(2):675-8
references.pmid: 2642903
references.citation: J Mol Biol. 2005 Mar 18;347(1):41-52
references.pmid: 15733916
references.citation: Mol Cell. 2006 Jun 23;22(6):843-850
references.pmid: 16793552
references.citation: Virology. 2000 Nov 25;277(2):450-6
references.pmid: 11080492
references.citation: J Virol. 2004 Mar;78(6):2897-905
references.pmid: 14990708
references.citation: Biophys J. 2006 Jul 1;91(1):42-54
references.pmid: 16565055
references.citation: Adv Virus Res. 1970;16:99-134
references.pmid: 4924992
references.citation: Nano Lett. 2005 Apr;5(4):765-70
references.pmid: 15826125
references.citation: J Am Chem Soc. 2012 May 30;134(21):8823-30
references.pmid: 22329660
references.citation: J Nanosci Nanotechnol. 2005 Dec;5(12):2029-33
references.pmid: 16430136
references.citation: Trends Microbiol. 2011 Jan;19(1):14-23
references.pmid: 21163649
references.citation: PLoS One. 2007 Aug 22;2(8):e765
references.pmid: 17712413
references.citation: J Am Chem Soc. 2006 Mar 1;128(8):2538-9
references.pmid: 16492029
references.citation: Bioessays. 2005 Apr;27(4):447-58
references.pmid: 15770675