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Virology1989; 170(1); 19-30; doi: 10.1016/0042-6822(89)90347-4

The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83.

Abstract: Nucleotide sequence analysis of cDNA clones covering the entire genomes of Trinidad donkey (TRD) Venezuelan equine encephalitis (VEE) virus and its vaccine derivative, TC-83, has revealed 11 differences between the genomes of TC-83 virus and its parent. One nucleotide substitution and a single nucleotide deletion occurred in the 5'- and 3'-noncoding regions of the TC-83 genome, respectively. The deduced amino acid sequences of the nonstructural polypeptides of the two viruses differed only in a conservative Ser(TRD) to Thr(TC-83) substitution in nonstructural protein (nsP) three at amino acid position 260. The two silent mutations (one each in E1 and E2), one amino acid substitution in the E1 glycoprotein, and five substitutions in the E2 envelope glycoprotein of TC-83 virus were reported previously (B.J.B. Johnson, R.M. Kinney, C.L. Kost, and D.W. Trent, 1986, J. Gen. Virol. 67, 1951-1960). The genome of TRD virus was 11,444 nucleotides long with a 5'-noncoding region of 44 nucleotides. The carboxyl terminal portion of VEE nsP3 contained two peptide segments (7 and 34 amino acids long) that were repeated with high fidelity. The open reading frame of the nonstructural polyprotein was interrupted by an in-frame opal termination codon between nsP3 and nsP4, as has been reported for Sindbis, Ross River, and Middelburg viruses. The deduced amino acid sequences of the VEE TRD nsP1, nsP2, nsP3, and nsP4 polypeptides showed 60-66%, 57-58%, 35-44%, and 73-71% identity with the aligned sequences of the cognate polypeptides of Sindbis and Semliki Forest viruses, respectively. The lack of homology in the nsP3 of the viruses is due to sequence variation in the carboxyl terminal half of this polypeptide.
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Publication Date: 1989-05-01 PubMed ID: 2524126DOI: 10.1016/0042-6822(89)90347-4Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied the full DNA sequences of a strain of the Trinidad donkey Venezuelan equine encephalitis virus and its TC-83 vaccine variant, identifying 11 differences between their genomes, including various substitutions and mutations.

Identified Differences in Genome

  • The researchers sequenced the complete genomes of the Trinidad donkey strain of the Venezuelan equine encephalitis virus and its vaccine derivative, strain TC-83.
  • In the process, they discovered a total of 11 differences between the two genomes. This included nucleotide substitutions and deletions, as well as singular and multiple amino acid substitutions.

Specific Changes in Genome

  • Specifically, there was a single nucleotide substitution and a single nucleotide deletion in the noncoding regions of the TC-83 genome.
  • The nonstructural proteins of the two viruses were almost identical barring a single conservative amino acid substitution in the nonstructural protein three.
  • Other mutations identified included two silent mutations in E1 and E2, an amino acid substitution in the E1 glycoprotein, and five substitutions in the E2 envelope glycoprotein of the TC-83 virus. These changes were previously reported in earlier studies.

TRD Virus Genome and Proteins

  • The analysis also revealed that the genome of the Trinidad Donkey (TRD) virus was 11,444 nucleotides long and had a noncoding region of 44 nucleotides.
  • The research also identified that the carboxyl terminal segment of the virus’s nonstructural protein 3 (nsP3) included two parts that were repeated with high fidelity.
  • The nonstructural polyprotein’s open reading frame was interrupted by an in-frame termination codon between nsP3 and nsP4, similar to Sindbis, Ross River, and Middelburg viruses.
  • Comparing the amino acid sequences of the nonstructural proteins of the VEE TRD virus to that of Sindbis and Semliki Forest viruses revealed percent identity ranges from 35% to 66%. The lowest homology was found in nsP3 due to sequence variation in the carboxyl terminal half of this polypeptide.

Significance of the Study

  • This research will help in understanding the fundamental DNA differences between the virulent strain of the Venezuelan equine encephalitis virus and its vaccine variant. This can aid in the development or improvement of vaccines for this and possibly other viruses.

Cite This Article

APA
Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW. (1989). The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83. Virology, 170(1), 19-30. https://doi.org/10.1016/0042-6822(89)90347-4

Publication

Virology
ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 170
Issue: 1
Pages: 19-30

Researcher Affiliations

Kinney, R M
  • Division of Vector-Borne Viral Diseases, Centers for Disease Control, Fort Collins, Colorado.
Johnson, B J
    Welch, J B
      Tsuchiya, K R
        Trent, D W

          MeSH Terms

          • Amino Acid Sequence
          • Animals
          • Base Sequence
          • Capsid / genetics
          • Encephalitis Virus, Venezuelan Equine / genetics
          • Genes, Viral
          • Molecular Sequence Data
          • Perissodactyla / microbiology
          • RNA, Viral / genetics
          • Viral Core Proteins / genetics
          • Viral Nonstructural Proteins
          • Viral Vaccines / genetics

          Citations

          This article has been cited 98 times.
          1. Liu H, Liu D. Development of novel SARS-CoV-2 viral vectors. Sci Rep 2023 Aug 11;13(1):13053.
            doi: 10.1038/s41598-023-40370-8pubmed: 37567900google scholar: lookup
          2. Amano T, Yu H, Amano M, Leyder E, Badiola M, Ray P, Kim J, Ko AC, Achour A, Weng NP, Kochba E, Levin Y, Ko MSH. Controllable self-replicating RNA vaccine delivered intradermally elicits predominantly cellular immunity. iScience 2023 Apr 21;26(4):106335.
            doi: 10.1016/j.isci.2023.106335pubmed: 36968065google scholar: lookup
          3. Wang H, Liu S, Lv Y, Wei W. Codon usage bias of Venezuelan equine encephalitis virus and its host adaption. Virus Res 2023 Apr 15;328:199081.
            doi: 10.1016/j.virusres.2023.199081pubmed: 36854361google scholar: lookup
          4. Babaeimarzangou SS, Zaker H, Soleimannezhadbari E, Gamchi NS, Kazeminia M, Tarighi S, Seyedian H, Tsatsakis A, Spandidos DA, Margina D. Vaccine development for zoonotic viral diseases caused by positive‑sense single‑stranded RNA viruses belonging to the Coronaviridae and Togaviridae families (Review). Exp Ther Med 2023 Jan;25(1):42.
            doi: 10.3892/etm.2022.11741pubmed: 36569444google scholar: lookup
          5. Sharp B, Rallabandi R, Devaux P. Advances in RNA Viral Vector Technology to Reprogram Somatic Cells: The Paramyxovirus Wave. Mol Diagn Ther 2022 Jul;26(4):353-367.
            doi: 10.1007/s40291-022-00599-xpubmed: 35763161google scholar: lookup
          6. Kafai NM, Williamson LE, Binshtein E, Sukupolvi-Petty S, Gardner CL, Liu J, Mackin S, Kim AS, Kose N, Carnahan RH, Jung A, Droit L, Reed DS, Handley SA, Klimstra WB, Crowe JE, Diamond MS. Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge. J Exp Med 2022 Apr 4;219(4).
            doi: 10.1084/jem.20212532pubmed: 35297953google scholar: lookup
          7. Li N, Chen XL, Li Q, Zhang ZR, Deng CL, Zhang B, Li XD, Ye HQ. A new screening system for entry inhibitors based on cell-to-cell transmitted syncytia formation mediated by self-propagating hybrid VEEV-SARS-CoV-2 replicon. Emerg Microbes Infect 2022 Dec;11(1):465-476.
            doi: 10.1080/22221751.2022.2030198pubmed: 35034586google scholar: lookup
          8. Ortega Granda O, Valle C, Shannon A, Decroly E, Canard B, Coutard B, Rabah N. Structure and Sequence Requirements for RNA Capping at the Venezuelan Equine Encephalitis Virus RNA 5' End. J Virol 2021 Jul 12;95(15):e0077721.
            doi: 10.1128/JVI.00777-21pubmed: 34011549google scholar: lookup
          9. Petkov S, Dressel R, Rodriguez-Polo I, Behr R. Controlling the Switch from Neurogenesis to Pluripotency during Marmoset Monkey Somatic Cell Reprogramming with Self-Replicating mRNAs and Small Molecules. Cells 2020 Nov 5;9(11).
            doi: 10.3390/cells9112422pubmed: 33167468google scholar: lookup
          10. Kim M, Hwang SU, Yoon JD, Jeong YW, Kim E, Hyun SH. Optimized Approaches for the Induction of Putative Canine Induced Pluripotent Stem Cells from Old Fibroblasts Using Synthetic RNAs. Animals (Basel) 2020 Oct 11;10(10).
            doi: 10.3390/ani10101848pubmed: 33050577google scholar: lookup
          11. Lee J, Parvathareddy J, Yang D, Bansal S, O'Connell K, Golden JE, Jonsson CB. Emergence and Magnitude of ML336 Resistance in Venezuelan Equine Encephalitis Virus Depend on the Microenvironment. J Virol 2020 Oct 27;94(22).
            doi: 10.1128/JVI.00317-20pubmed: 32878897google scholar: lookup
          12. Stromberg ZR, Fischer W, Bradfute SB, Kubicek-Sutherland JZ, Hraber P. Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses. Vaccines (Basel) 2020 Jun 3;8(2).
            doi: 10.3390/vaccines8020273pubmed: 32503232google scholar: lookup
          13. Patterson EI, Khanipov K, Swetnam DM, Walsdorf S, Kautz TF, Thangamani S, Fofanov Y, Forrester NL. Measuring Alphavirus Fidelity Using Non-Infectious Virus Particles. Viruses 2020 May 15;12(5).
            doi: 10.3390/v12050546pubmed: 32429270google scholar: lookup
          14. He W, Evans AC, Rasley A, Bourguet F, Peters S, Kamrud KI, Wang N, Hubby B, Felderman M, Gouvis H, Coleman MA, Fischer NO. Cationic HDL mimetics enhance in vivo delivery of self-replicating mRNA. Nanomedicine 2020 Feb;24:102154.
            doi: 10.1016/j.nano.2020.102154pubmed: 31982617google scholar: lookup
          15. Meshram CD, Phillips AT, Lukash T, Shiliaev N, Frolova EI, Frolov I. Mutations in Hypervariable Domain of Venezuelan Equine Encephalitis Virus nsP3 Protein Differentially Affect Viral Replication. J Virol 2020 Jan 17;94(3).
            doi: 10.1128/JVI.01841-19pubmed: 31694937google scholar: lookup
          16. Meshram CD, Lukash T, Phillips AT, Akhrymuk I, Frolova EI, Frolov I. Lack of nsP2-specific nuclear functions attenuates chikungunya virus replication both in vitro and in vivo. Virology 2019 Aug;534:14-24.
            doi: 10.1016/j.virol.2019.05.016pubmed: 31163352google scholar: lookup
          17. Sharma A, Knollmann-Ritschel B. Current Understanding of the Molecular Basis of Venezuelan Equine Encephalitis Virus Pathogenesis and Vaccine Development. Viruses 2019 Feb 18;11(2).
            doi: 10.3390/v11020164pubmed: 30781656google scholar: lookup
          18. Kautz TF, Guerbois M, Khanipov K, Patterson EI, Langsjoen RM, Yun R, Warmbrod KL, Fofanov Y, Weaver SC, Forrester NL. Low-fidelity Venezuelan equine encephalitis virus polymerase mutants to improve live-attenuated vaccine safety and efficacy. Virus Evol 2018 Jan;4(1):vey004.
            doi: 10.1093/ve/vey004pubmed: 29593882google scholar: lookup
          19. Yoshioka N, Dowdy SF. Enhanced generation of iPSCs from older adult human cells by a synthetic five-factor self-replicative RNA. PLoS One 2017;12(7):e0182018.
            doi: 10.1371/journal.pone.0182018pubmed: 28750082google scholar: lookup
          20. Shen Y, Huang J, Liu L, Xu X, Han C, Zhang G, Jiang H, Li J, Lin Z, Xiong N, Wang T. A Compendium of Preparation and Application of Stem Cells in Parkinson's Disease: Current Status and Future Prospects. Front Aging Neurosci 2016;8:117.
            doi: 10.3389/fnagi.2016.00117pubmed: 27303288google scholar: lookup
          21. Amaya M, Keck F, Lindquist M, Voss K, Scavone L, Kehn-Hall K, Roberts B, Bailey C, Schmaljohn C, Narayanan A. The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection. PLoS One 2015;10(4):e0124792.
            doi: 10.1371/journal.pone.0124792pubmed: 25927990google scholar: lookup
          22. Reynaud JM, Kim DY, Atasheva S, Rasalouskaya A, White JP, Diamond MS, Weaver SC, Frolova EI, Frolov I. IFIT1 Differentially Interferes with Translation and Replication of Alphavirus Genomes and Promotes Induction of Type I Interferon. PLoS Pathog 2015 Apr;11(4):e1004863.
            doi: 10.1371/journal.ppat.1004863pubmed: 25927359google scholar: lookup
          23. Hyde JL, Diamond MS. Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation. Virology 2015 May;479-480:66-74.
            doi: 10.1016/j.virol.2015.01.019pubmed: 25682435google scholar: lookup
          24. Hyde JL, Chen R, Trobaugh DW, Diamond MS, Weaver SC, Klimstra WB, Wilusz J. The 5' and 3' ends of alphavirus RNAs--Non-coding is not non-functional. Virus Res 2015 Aug 3;206:99-107.
            doi: 10.1016/j.virusres.2015.01.016pubmed: 25630058google scholar: lookup
          25. Atasheva S, Kim DY, Frolova EI, Frolov I. Venezuelan equine encephalitis virus variants lacking transcription inhibitory functions demonstrate highly attenuated phenotype. J Virol 2015 Jan;89(1):71-82.
            doi: 10.1128/JVI.02252-14pubmed: 25320296google scholar: lookup
          26. Go YY, Balasuriya UB, Lee CK. Zoonotic encephalitides caused by arboviruses: transmission and epidemiology of alphaviruses and flaviviruses. Clin Exp Vaccine Res 2014 Jan;3(1):58-77.
            doi: 10.7774/cevr.2014.3.1.58pubmed: 24427764google scholar: lookup
          27. Lulla V, Kim DY, Frolova EI, Frolov I. The amino-terminal domain of alphavirus capsid protein is dispensable for viral particle assembly but regulates RNA encapsidation through cooperative functions of its subdomains. J Virol 2013 Nov;87(22):12003-19.
            doi: 10.1128/JVI.01960-13pubmed: 24006447google scholar: lookup
          28. Yoshioka N, Gros E, Li HR, Kumar S, Deacon DC, Maron C, Muotri AR, Chi NC, Fu XD, Yu BD, Dowdy SF. Efficient generation of human iPSCs by a synthetic self-replicative RNA. Cell Stem Cell 2013 Aug 1;13(2):246-54.
            doi: 10.1016/j.stem.2013.06.001pubmed: 23910086google scholar: lookup
          29. Guerbois M, Volkova E, Forrester NL, Rossi SL, Frolov I, Weaver SC. IRES-driven expression of the capsid protein of the Venezuelan equine encephalitis virus TC-83 vaccine strain increases its attenuation and safety. PLoS Negl Trop Dis 2013;7(5):e2197.
            doi: 10.1371/journal.pntd.0002197pubmed: 23675542google scholar: lookup
          30. Diaz-San Segundo F, Dias CC, Moraes MP, Weiss M, Perez-Martin E, Owens G, Custer M, Kamrud K, de los Santos T, Grubman MJ. Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus. J Virol 2013 May;87(10):5447-60.
            doi: 10.1128/JVI.03462-12pubmed: 23468490google scholar: lookup
          31. Peng BH, Borisevich V, Popov VL, Zacks MA, Estes DM, Campbell GA, Paessler S. Production of IL-8, IL-17, IFN-gamma and IP-10 in human astrocytes correlates with alphavirus attenuation. Vet Microbiol 2013 May 3;163(3-4):223-34.
            doi: 10.1016/j.vetmic.2012.11.021pubmed: 23428380google scholar: lookup
          32. Kim DY, Atasheva S, Frolova EI, Frolov I. Venezuelan equine encephalitis virus nsP2 protein regulates packaging of the viral genome into infectious virions. J Virol 2013 Apr;87(8):4202-13.
            doi: 10.1128/JVI.03142-12pubmed: 23365438google scholar: lookup
          33. Rossi SL, Guerbois M, Gorchakov R, Plante KS, Forrester NL, Weaver SC. IRES-based Venezuelan equine encephalitis vaccine candidate elicits protective immunity in mice. Virology 2013 Mar 15;437(2):81-8.
            doi: 10.1016/j.virol.2012.11.013pubmed: 23351391google scholar: lookup
          34. Atasheva S, Kim DY, Akhrymuk M, Morgan DG, Frolova EI, Frolov I. Pseudoinfectious Venezuelan equine encephalitis virus: a new means of alphavirus attenuation. J Virol 2013 Feb;87(4):2023-35.
            doi: 10.1128/JVI.02881-12pubmed: 23221545google scholar: lookup
          35. Pandya J, Gorchakov R, Wang E, Leal G, Weaver SC. A vaccine candidate for eastern equine encephalitis virus based on IRES-mediated attenuation. Vaccine 2012 Feb 8;30(7):1276-82.
            doi: 10.1016/j.vaccine.2011.12.121pubmed: 22222869google scholar: lookup
          36. Patterson M, Poussard A, Taylor K, Seregin A, Smith J, Peng BH, Walker A, Linde J, Smith J, Salazar M, Paessler S. Rapid, non-invasive imaging of alphaviral brain infection: reducing animal numbers and morbidity to identify efficacy of potential vaccines and antivirals. Vaccine 2011 Nov 21;29(50):9345-51.
            doi: 10.1016/j.vaccine.2011.09.130pubmed: 22001884google scholar: lookup
          37. Kenney JL, Volk SM, Pandya J, Wang E, Liang X, Weaver SC. Stability of RNA virus attenuation approaches. Vaccine 2011 Mar 9;29(12):2230-4.
            doi: 10.1016/j.vaccine.2011.01.055pubmed: 21288800google scholar: lookup
          38. Hooper JW, Ferro AM, Golden JW, Silvera P, Dudek J, Alterson K, Custer M, Rivers B, Morris J, Owens G, Smith JF, Kamrud KI. Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates. Vaccine 2009 Dec 11;28(2):494-511.
            doi: 10.1016/j.vaccine.2009.09.133pubmed: 19833247google scholar: lookup
          39. Martin SS, Bakken RR, Lind CM, Reed DS, Price JL, Koeller CA, Parker MD, Hart MK, Fine DL. Telemetric analysis to detect febrile responses in mice following vaccination with a live-attenuated virus vaccine. Vaccine 2009 Nov 16;27(49):6814-23.
            doi: 10.1016/j.vaccine.2009.09.013pubmed: 19761841google scholar: lookup
          40. Frolov I, Garmashova N, Atasheva S, Frolova EI. Random insertion mutagenesis of sindbis virus nonstructural protein 2 and selection of variants incapable of downregulating cellular transcription. J Virol 2009 Sep;83(18):9031-44.
            doi: 10.1128/JVI.00850-09pubmed: 19570872google scholar: lookup
          41. Kulasegaran-Shylini R, Atasheva S, Gorenstein DG, Frolov I. Structural and functional elements of the promoter encoded by the 5' untranslated region of the Venezuelan equine encephalitis virus genome. J Virol 2009 Sep;83(17):8327-39.
            doi: 10.1128/JVI.00586-09pubmed: 19515761google scholar: lookup
          42. Kulasegaran-Shylini R, Thiviyanathan V, Gorenstein DG, Frolov I. The 5'UTR-specific mutation in VEEV TC-83 genome has a strong effect on RNA replication and subgenomic RNA synthesis, but not on translation of the encoded proteins. Virology 2009 Apr 25;387(1):211-21.
            doi: 10.1016/j.virol.2009.02.027pubmed: 19278709google scholar: lookup
          43. Gorchakov R, Garmashova N, Frolova E, Frolov I. Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 2008 Oct;82(20):10088-101.
            doi: 10.1128/JVI.01011-08pubmed: 18684830google scholar: lookup
          44. Volkova E, Frolova E, Darwin JR, Forrester NL, Weaver SC, Frolov I. IRES-dependent replication of Venezuelan equine encephalitis virus makes it highly attenuated and incapable of replicating in mosquito cells. Virology 2008 Jul 20;377(1):160-9.
            doi: 10.1016/j.virol.2008.04.020pubmed: 18501401google scholar: lookup
          45. Paessler S, Rijnbrand R, Stein DA, Ni H, Yun NE, Dziuba N, Borisevich V, Seregin A, Ma Y, Blouch R, Iversen PL, Zacks MA. Inhibition of alphavirus infection in cell culture and in mice with antisense morpholino oligomers. Virology 2008 Jul 5;376(2):357-70.
            doi: 10.1016/j.virol.2008.03.032pubmed: 18468653google scholar: lookup
          46. Gorchakov R, Frolova E, Sawicki S, Atasheva S, Sawicki D, Frolov I. A new role for ns polyprotein cleavage in Sindbis virus replication. J Virol 2008 Jul;82(13):6218-31.
            doi: 10.1128/JVI.02624-07pubmed: 18417571google scholar: lookup
          47. Garmashova N, Atasheva S, Kang W, Weaver SC, Frolova E, Frolov I. Analysis of Venezuelan equine encephalitis virus capsid protein function in the inhibition of cellular transcription. J Virol 2007 Dec;81(24):13552-65.
            doi: 10.1128/JVI.01576-07pubmed: 17913819google scholar: lookup
          48. Gorchakov R, Volkova E, Yun N, Petrakova O, Linde NS, Paessler S, Frolova E, Frolov I. Comparative analysis of the alphavirus-based vectors expressing Rift Valley fever virus glycoproteins. Virology 2007 Sep 15;366(1):212-25.
            doi: 10.1016/j.virol.2007.04.014pubmed: 17507072google scholar: lookup
          49. Atasheva S, Gorchakov R, English R, Frolov I, Frolova E. Development of Sindbis viruses encoding nsP2/GFP chimeric proteins and their application for studying nsP2 functioning. J Virol 2007 May;81(10):5046-57.
            doi: 10.1128/JVI.02746-06pubmed: 17329335google scholar: lookup
          50. Michel G, Petrakova O, Atasheva S, Frolov I. Adaptation of Venezuelan equine encephalitis virus lacking 51-nt conserved sequence element to replication in mammalian and mosquito cells. Virology 2007 Jun 5;362(2):475-87.
            doi: 10.1016/j.virol.2007.01.009pubmed: 17292936google scholar: lookup
          51. Garmashova N, Gorchakov R, Volkova E, Paessler S, Frolova E, Frolov I. The Old World and New World alphaviruses use different virus-specific proteins for induction of transcriptional shutoff. J Virol 2007 Mar;81(5):2472-84.
            doi: 10.1128/JVI.02073-06pubmed: 17108023google scholar: lookup
          52. Wang E, Paessler S, Aguilar PV, Carrara AS, Ni H, Greene IP, Weaver SC. Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections. J Clin Microbiol 2006 Nov;44(11):4000-8.
            doi: 10.1128/JCM.00175-06pubmed: 16957044google scholar: lookup
          53. Frolova E, Gorchakov R, Garmashova N, Atasheva S, Vergara LA, Frolov I. Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol 2006 Apr;80(8):4122-34.
            doi: 10.1128/JVI.80.8.4122-4134.2006pubmed: 16571828google scholar: lookup
          54. Anishchenko M, Bowen RA, Paessler S, Austgen L, Greene IP, Weaver SC. Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation. Proc Natl Acad Sci U S A 2006 Mar 28;103(13):4994-9.
            doi: 10.1073/pnas.0509961103pubmed: 16549790google scholar: lookup
          55. Thompson JM, Whitmore AC, Konopka JL, Collier ML, Richmond EM, Davis NL, Staats HF, Johnston RE. Mucosal and systemic adjuvant activity of alphavirus replicon particles. Proc Natl Acad Sci U S A 2006 Mar 7;103(10):3722-7.
            doi: 10.1073/pnas.0600287103pubmed: 16505353google scholar: lookup
          56. Navarro JC, Medina G, Vasquez C, Coffey LL, Wang E, Suárez A, Biord H, Salas M, Weaver SC. Postepizootic persistence of Venezuelan equine encephalitis virus, Venezuela. Emerg Infect Dis 2005 Dec;11(12):1907-15.
            doi: 10.3201/eid1112.050533pubmed: 16485478google scholar: lookup
          57. Volkova E, Gorchakov R, Frolov I. The efficient packaging of Venezuelan equine encephalitis virus-specific RNAs into viral particles is determined by nsP1-3 synthesis. Virology 2006 Jan 20;344(2):315-27.
            doi: 10.1016/j.virol.2005.09.010pubmed: 16239019google scholar: lookup
          58. Greene IP, Paessler S, Austgen L, Anishchenko M, Brault AC, Bowen RA, Weaver SC. Envelope glycoprotein mutations mediate equine amplification and virulence of epizootic venezuelan equine encephalitis virus. J Virol 2005 Jul;79(14):9128-33.
            doi: 10.1128/JVI.79.14.9128-9133.2005pubmed: 15994807google scholar: lookup
          59. Petrakova O, Volkova E, Gorchakov R, Paessler S, Kinney RM, Frolov I. Noncytopathic replication of Venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in Mammalian cells. J Virol 2005 Jun;79(12):7597-608.
            doi: 10.1128/JVI.79.12.7597-7608.2005pubmed: 15919912google scholar: lookup
          60. Fayzulin R, Frolov I. Changes of the secondary structure of the 5' end of the Sindbis virus genome inhibit virus growth in mosquito cells and lead to accumulation of adaptive mutations. J Virol 2004 May;78(10):4953-64.
            doi: 10.1128/jvi.78.10.4953-4964.2004pubmed: 15113874google scholar: lookup
          61. Perri S, Greer CE, Thudium K, Doe B, Legg H, Liu H, Romero RE, Tang Z, Bin Q, Dubensky TW Jr, Vajdy M, Otten GR, Polo JM. An alphavirus replicon particle chimera derived from venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol 2003 Oct;77(19):10394-403.
            doi: 10.1128/jvi.77.19.10394-10403.2003pubmed: 12970424google scholar: lookup
          62. Paessler S, Fayzulin RZ, Anishchenko M, Greene IP, Weaver SC, Frolov I. Recombinant sindbis/Venezuelan equine encephalitis virus is highly attenuated and immunogenic. J Virol 2003 Sep;77(17):9278-86.
            doi: 10.1128/jvi.77.17.9278-9286.2003pubmed: 12915543google scholar: lookup
          63. Gonzalez-Salazar D, Estrada-Franco JG, Carrara AS, Aronson JF, Weaver SC. Equine amplification and virulence of subtype IE Venezuelan equine encephalitis viruses isolated during the 1993 and 1996 Mexican epizootics. Emerg Infect Dis 2003 Feb;9(2):161-8.
            doi: 10.3201/eid0902.020124pubmed: 12603985google scholar: lookup
          64. Paredes A, Alwell-Warda K, Weaver SC, Chiu W, Watowich SJ. Structure of isolated nucleocapsids from venezuelan equine encephalitis virus and implications for assembly and disassembly of enveloped virus. J Virol 2003 Jan;77(1):659-64.
            doi: 10.1128/jvi.77.1.659-664.2003pubmed: 12477868google scholar: lookup
          65. Fata CL, Sawicki SG, Sawicki DL. Alphavirus minus-strand RNA synthesis: identification of a role for Arg183 of the nsP4 polymerase. J Virol 2002 Sep;76(17):8632-40.
            doi: 10.1128/jvi.76.17.8632-8640.2002pubmed: 12163582google scholar: lookup
          66. Brault AC, Powers AM, Holmes EC, Woelk CH, Weaver SC. Positively charged amino acid substitutions in the e2 envelope glycoprotein are associated with the emergence of venezuelan equine encephalitis virus. J Virol 2002 Feb;76(4):1718-30.
            doi: 10.1128/jvi.76.4.1718-1730.2002pubmed: 11799167google scholar: lookup
          67. Powers AM, Brault AC, Shirako Y, Strauss EG, Kang W, Strauss JH, Weaver SC. Evolutionary relationships and systematics of the alphaviruses. J Virol 2001 Nov;75(21):10118-31.
            doi: 10.1128/JVI.75.21.10118-10131.2001pubmed: 11581380google scholar: lookup
          68. Paredes A, Alwell-Warda K, Weaver SC, Chiu W, Watowich SJ. Venezuelan equine encephalomyelitis virus structure and its divergence from old world alphaviruses. J Virol 2001 Oct;75(19):9532-7.
            doi: 10.1128/JVI.75.19.9532-9537.2001pubmed: 11533216google scholar: lookup
          69. Brault AC, Powers AM, Medina G, Wang E, Kang W, Salas RA, De Siger J, Weaver SC. Potential sources of the 1995 Venezuelan equine encephalitis subtype IC epidemic. J Virol 2001 Jul;75(13):5823-32.
            doi: 10.1128/JVI.75.13.5823-5832.2001pubmed: 11390583google scholar: lookup
          70. White LJ, Wang JG, Davis NL, Johnston RE. Role of alpha/beta interferon in Venezuelan equine encephalitis virus pathogenesis: effect of an attenuating mutation in the 5' untranslated region. J Virol 2001 Apr;75(8):3706-18.
            doi: 10.1128/JVI.75.8.3706-3718.2001pubmed: 11264360google scholar: lookup
          71. Tuittila MT, Santagati MG, Röyttä M, Määttä JA, Hinkkanen AE. Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 2000 May;74(10):4579-89.
            doi: 10.1128/jvi.74.10.4579-4589.2000pubmed: 10775594google scholar: lookup
          72. Powers AM, Brault AC, Kinney RM, Weaver SC. The use of chimeric Venezuelan equine encephalitis viruses as an approach for the molecular identification of natural virulence determinants. J Virol 2000 May;74(9):4258-63.
            doi: 10.1128/jvi.74.9.4258-4263.2000pubmed: 10756040google scholar: lookup
          73. Meissner JD, Huang CY, Pfeffer M, Kinney RM. Sequencing of prototype viruses in the Venezuelan equine encephalitis antigenic complex. Virus Res 1999 Oct;64(1):43-59.
            doi: 10.1016/s0168-1702(99)00078-7pubmed: 10500282google scholar: lookup
          74. Frolov I, Agapov E, Hoffman TA Jr, Prágai BM, Lippa M, Schlesinger S, Rice CM. Selection of RNA replicons capable of persistent noncytopathic replication in mammalian cells. J Virol 1999 May;73(5):3854-65.
            doi: 10.1128/JVI.73.5.3854-3865.1999pubmed: 10196280google scholar: lookup
          75. Swanson MM, Ansel-McKinney P, Houser-Scott F, Yusibov V, Loesch-Fries LS, Gehrke L. Viral coat protein peptides with limited sequence homology bind similar domains of alfalfa mosaic virus and tobacco streak virus RNAs. J Virol 1998 Apr;72(4):3227-34.
            doi: 10.1128/JVI.72.4.3227-3234.1998pubmed: 9525649google scholar: lookup
          76. Powers AM, Oberste MS, Brault AC, Rico-Hesse R, Schmura SM, Smith JF, Kang W, Sweeney WP, Weaver SC. Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a single genotype of enzootic subtype ID virus. J Virol 1997 Sep;71(9):6697-705.
            doi: 10.1128/JVI.71.9.6697-6705.1997pubmed: 9261393google scholar: lookup
          77. Dubuisson J, Lustig S, Ruggli N, Akov Y, Rice CM. Genetic determinants of Sindbis virus neuroinvasiveness. J Virol 1997 Apr;71(4):2636-46.
            doi: 10.1128/JVI.71.4.2636-2646.1997pubmed: 9060616google scholar: lookup
          78. Pereboev AV, Razumov IA, Svyatchenko VA, Loktev VB. Glycoproteins E2 of the Venezuelan and eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes. Arch Virol 1996;141(11):2191-205.
            doi: 10.1007/BF01718225pubmed: 8973533google scholar: lookup
          79. Ansel-McKinney P, Scott SW, Swanson M, Ge X, Gehrke L. A plant viral coat protein RNA binding consensus sequence contains a crucial arginine. EMBO J 1996 Sep 16;15(18):5077-84.
            pubmed: 8890181
          80. Baklanov MM, Golikova LN, Malygin EG. Effect on DNA transcription of nucleotide sequences upstream to T7 promoter. Nucleic Acids Res 1996 Sep 15;24(18):3659-60.
            doi: 10.1093/nar/24.18.3659pubmed: 8836202google scholar: lookup
          81. Urban C, Zerfass K, Fingerhut C, Beier H. UGA suppression by tRNACmCATrp occurs in diverse virus RNAs due to a limited influence of the codon context. Nucleic Acids Res 1996 Sep 1;24(17):3424-30.
            doi: 10.1093/nar/24.17.3424pubmed: 8811098google scholar: lookup
          82. Sawicki DL, Sawicki SG. A second nonstructural protein functions in the regulation of alphavirus negative-strand RNA synthesis. J Virol 1993 Jun;67(6):3605-10.
            doi: 10.1128/JVI.67.6.3605-3610.1993pubmed: 8388513google scholar: lookup
          83. Weaver SC, Hagenbaugh A, Bellew LA, Gousset L, Mallampalli V, Holland JJ, Scott TW. Evolution of alphaviruses in the eastern equine encephalomyelitis complex. J Virol 1994 Jan;68(1):158-69.
            doi: 10.1128/JVI.68.1.158-169.1994pubmed: 8254725google scholar: lookup
          84. Wang YF, Sawicki SG, Sawicki DL. Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA. J Virol 1994 Oct;68(10):6466-75.
            doi: 10.1128/JVI.68.10.6466-6475.1994pubmed: 8083984google scholar: lookup
          85. LaStarza MW, Lemm JA, Rice CM. Genetic analysis of the nsP3 region of Sindbis virus: evidence for roles in minus-strand and subgenomic RNA synthesis. J Virol 1994 Sep;68(9):5781-91.
            doi: 10.1128/JVI.68.9.5781-5791.1994pubmed: 8057460google scholar: lookup
          86. Strauss JH, Strauss EG. The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 1994 Sep;58(3):491-562.
            doi: 10.1128/mr.58.3.491-562.1994pubmed: 7968923google scholar: lookup
          87. Rico-Hesse R, Weaver SC, de Siger J, Medina G, Salas RA. Emergence of a new epidemic/epizootic Venezuelan equine encephalitis virus in South America. Proc Natl Acad Sci U S A 1995 Jun 6;92(12):5278-81.
            doi: 10.1073/pnas.92.12.5278pubmed: 7777497google scholar: lookup
          88. Kinney RM, Chang GJ, Tsuchiya KR, Sneider JM, Roehrig JT, Woodward TM, Trent DW. Attenuation of Venezuelan equine encephalitis virus strain TC-83 is encoded by the 5'-noncoding region and the E2 envelope glycoprotein. J Virol 1993 Mar;67(3):1269-77.
            doi: 10.1128/JVI.67.3.1269-1277.1993pubmed: 7679745google scholar: lookup
          89. Hardy WR, Strauss JH. Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J Virol 1989 Nov;63(11):4653-64.
            doi: 10.1128/JVI.63.11.4653-4664.1989pubmed: 2529379google scholar: lookup
          90. Niesters HG, Strauss JH. Mutagenesis of the conserved 51-nucleotide region of Sindbis virus. J Virol 1990 Apr;64(4):1639-47.
            doi: 10.1128/JVI.64.4.1639-1647.1990pubmed: 2319648google scholar: lookup
          91. Lemm JA, Durbin RK, Stollar V, Rice CM. Mutations which alter the level or structure of nsP4 can affect the efficiency of Sindbis virus replication in a host-dependent manner. J Virol 1990 Jun;64(6):3001-11.
            doi: 10.1128/JVI.64.6.3001-3011.1990pubmed: 2159558google scholar: lookup
          92. Liljeström P, Garoff H. Internally located cleavable signal sequences direct the formation of Semliki Forest virus membrane proteins from a polyprotein precursor. J Virol 1991 Jan;65(1):147-54.
            doi: 10.1128/JVI.65.1.147-154.1991pubmed: 1985194google scholar: lookup
          93. LaPointe AT, Ferrara F, Zupancic JM, Montoya AL, Schmidt J, Hung LW, Kell AM, Velappan N. Discovering Novel Therapeutic V(H)Hs for Emerging Viruses: Perspectives from VEEV Selection Strategies. bioRxiv 2026 Jan 26;.
            doi: 10.64898/2026.01.24.701463pubmed: 41659433google scholar: lookup
          94. Casmil IC, Jin J, Won EJ, Huang C, Liao S, Cha-Molstad H, Blakney AK. The advent of clinical self-amplifying RNA vaccines. Mol Ther 2025 Jun 4;33(6):2565-2582.
            doi: 10.1016/j.ymthe.2025.03.060pubmed: 40186353google scholar: lookup
          95. Williams EP, Xue Y, Vogel P, Yang D, Ponce-Flores A, Li X, Ogorek TJ, Saini M, Iulek J, Ruiz FX, Arnold E, Golden JE, Meibohm B, Jonsson CB. The antiviral BDGR-49 provides protection from lethal, neurotropic Venezuelan equine encephalitis virus intranasal infection in mice. J Virol 2025 Mar 18;99(3):e0167924.
            doi: 10.1128/jvi.01679-24pubmed: 39936916google scholar: lookup
          96. Hickson SE, Hyde JL. RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence. PLoS Pathog 2024 Sep;20(9):e1012179.
            doi: 10.1371/journal.ppat.1012179pubmed: 39331659google scholar: lookup
          97. Hickson SE, Hyde JL. RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence. bioRxiv 2024 Apr 9;.
            doi: 10.1101/2024.04.09.588743pubmed: 38645187google scholar: lookup
          98. Williams EP, Xue Y, Lee J, Fitzpatrick EA, Kong Y, Reichard W, Writt H, Jonsson CB. Deep spatial profiling of Venezuelan equine encephalitis virus reveals increased genetic diversity amidst neuroinflammation and cell death during brain infection. J Virol 2023 Aug 31;97(8):e0082723.
            doi: 10.1128/jvi.00827-23pubmed: 37560924google scholar: lookup
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