FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PLoS One / A single amino acid substitution in the core protein of West...
PloS one2013; 8(7); e69479; doi: 10.1371/journal.pone.0069479

A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds.

Abstract: West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that naturally cycles between birds and mosquitoes, although it can infect multiple vertebrate hosts including horses and humans. This virus is responsible for recurrent epidemics of febrile illness and encephalitis, and has recently become a global concern. WNV requires to transit through intracellular acidic compartments at two different steps to complete its infectious cycle. These include fusion between the viral envelope and the membrane of endosomes during viral entry, and virus maturation in the trans-Golgi network. In this study, we followed a genetic approach to study the connections between viral components and acidic pH. A WNV mutant with increased resistance to the acidotropic compound NH4Cl, which blocks organelle acidification and inhibits WNV infection, was selected. Nucleotide sequencing revealed that this mutant displayed a single amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or core (C) protein. The functional role of this replacement was confirmed by its introduction into a WNV infectious clone. This single amino acid substitution also increased resistance to other acidification inhibitor (concanamycin A) and induced a reduction of the neurovirulence in mice. Interestingly, a naturally occurring accompanying mutation found on prM protein abolished the resistant phenotype, supporting the idea of a genetic crosstalk between the internal C protein and the external glycoproteins of the virion. The findings here reported unveil a non-previously assessed connection between the C viral protein and the acidic pH necessary for entry and proper exit of flaviviruses.
Get Full Text
Publication Date: 2013-07-18 PubMed ID: 23874963PubMed Central: PMC3715472DOI: 10.1371/journal.pone.0069479Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The research article discusses a study investigating the relationship between West Nile virus (WNV) innate resistance to certain acidic compounds and a specific genetic mutation. The researchers have identified that a single amino acid change in the internal core protein of WNV significantly enhances the virus’s resistance to acidic environments.

Study Overview

  • The study focused on West Nile virus (WNV), a mosquito-borne flavivirus, which cycles between birds and mosquitoes, but can also infect a host of other vertebrates, including humans and horses. WNV is a cause of global concern due to recurrent epidemics of febrile illness and encephalitis it triggers.
  • To complete its infectious cycle, WNV passes through two key intracellular acidic compartments: viral envelope fusion with endosomes membrane during viral entry, and virus maturation in the trans-Golgi network.

Research Methodology

  • The researchers utilized a genetic approach to explore the correlation between viral components and acidic pH.
  • They selected a WNV mutant that demonstrated increased resistance to NH4Cl, an acidotropic compound that blocks organelle acidification and consequently impedes WNV infection.
  • DNA sequencing of this mutant revealed it had a single amino acid change (from Lysine 3 to Glutamate) in the highly basic internal capsid or core protein.

Important Finding

  • The research confirmed the functional role of this amino acid replacement by introducing it into a WNV infectious clone.
  • Apart from increasing resistance to other acidification inhibitors (like concanamycin A), this mutation also resulted in a reduction in the virus’s neurovirulence in mice.
  • Interestingly, a naturally occurring mutation discovered in the prM protein nullified this resistance, which suggests a genetic interaction or ‘crosstalk’ between the internal core protein and the external glycoproteins of the virion.

Significance

  • This study reveals a previously unnoticed connection between the C viral protein and the acidic pH crucial for the virus’s entry and appropriate exit from host cells.
  • This groundbreaking understanding could contribute significantly to developing new treatment strategies for diseases caused by flaviviruses, including the West Nile virus.

Cite This Article

APA
Martín-Acebes MA, Blázquez AB, de Oya NJ, Escribano-Romero E, Shi PY, Saiz JC. (2013). A single amino acid substitution in the core protein of West Nile virus increases resistance to acidotropic compounds. PLoS One, 8(7), e69479. https://doi.org/10.1371/journal.pone.0069479

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 7
Pages: e69479
PII: e69479

Researcher Affiliations

Martín-Acebes, Miguel A
  • Departamento de Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain. martin.mangel@inia.es
Blázquez, Ana-Belén
    de Oya, Nereida Jiménez
      Escribano-Romero, Estela
        Shi, Pei-Yong
          Saiz, Juan-Carlos

            MeSH Terms

            • Amino Acid Substitution / genetics
            • Ammonium Chloride / pharmacology
            • Analysis of Variance
            • Animals
            • Blotting, Western
            • Chlorocebus aethiops
            • Cricetinae
            • Drug Resistance, Viral / genetics
            • Fluorescent Antibody Technique
            • Hydrogen-Ion Concentration
            • Macrolides / pharmacology
            • Mice
            • Real-Time Polymerase Chain Reaction
            • Reverse Transcriptase Polymerase Chain Reaction
            • Vero Cells
            • Viral Core Proteins / genetics
            • Virulence
            • West Nile virus / genetics
            • West Nile virus / pathogenicity

            Conflict of Interest Statement

            The authors have declared that no competing interests exist.

            References

            This article includes 85 references
            1. Beasley DW. Recent advances in the molecular biology of west nile virus.. Curr Mol Med 2005 Dec;5(8):835-50.
              pubmed: 16375717doi: 10.2174/156652405774962272google scholar: lookup
            2. Brinton MA. The molecular biology of West Nile Virus: a new invader of the western hemisphere.. Annu Rev Microbiol 2002;56:371-402.
              pubmed: 12142476doi: 10.1146/annurev.micro.56.012302.160654google scholar: lookup
            3. Martín-Acebes MA, Saiz JC. West Nile virus: A re-emerging pathogen revisited.. World J Virol 2012 Apr 12;1(2):51-70.
              pmc: PMC3782267pubmed: 24175211doi: 10.5501/wjv.v1.i2.51google scholar: lookup
            4. Hayes EB, Gubler DJ. West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States.. Annu Rev Med 2006;57:181-94.
              pubmed: 16409144doi: 10.1146/annurev.med.57.121304.131418google scholar: lookup
            5. Brault AC. Changing patterns of West Nile virus transmission: altered vector competence and host susceptibility.. Vet Res 2009 Mar-Apr;40(2):43.
              pmc: PMC2695027pubmed: 19406093doi: 10.1051/vetres/2009026google scholar: lookup
            6. Kilpatrick AM. Globalization, land use, and the invasion of West Nile virus.. Science 2011 Oct 21;334(6054):323-7.
              pmc: PMC3346291pubmed: 22021850doi: 10.1126/science.1201010google scholar: lookup
            7. Kramer LD, Styer LM, Ebel GD. A global perspective on the epidemiology of West Nile virus.. Annu Rev Entomol 2008;53:61-81.
              pubmed: 17645411doi: 10.1146/annurev.ento.53.103106.093258google scholar: lookup
            8. Petersen LR, Carson PJ, Biggerstaff BJ, Custer B, Borchardt SM, Busch MP. Estimated cumulative incidence of West Nile virus infection in US adults, 1999-2010.. Epidemiol Infect 2013 Mar;141(3):591-5.
              pmc: PMC9151873pubmed: 22640592doi: 10.1017/S0950268812001070google scholar: lookup
            9. Diamond MS. Progress on the development of therapeutics against West Nile virus.. Antiviral Res 2009 Sep;83(3):214-27.
              pmc: PMC2759769pubmed: 19501622doi: 10.1016/j.antiviral.2009.05.006google scholar: lookup
            10. Lanciotti RS, Roehrig JT, Deubel V, Smith J, Parker M, Steele K, Crise B, Volpe KE, Crabtree MB, Scherret JH, Hall RA, MacKenzie JS, Cropp CB, Panigrahy B, Ostlund E, Schmitt B, Malkinson M, Banet C, Weissman J, Komar N, Savage HM, Stone W, McNamara T, Gubler DJ. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States.. Science 1999 Dec 17;286(5448):2333-7.
              pubmed: 10600742doi: 10.1126/science.286.5448.2333google scholar: lookup
            11. Mukhopadhyay S, Kim BS, Chipman PR, Rossmann MG, Kuhn RJ. Structure of West Nile virus.. Science 2003 Oct 10;302(5643):248.
              pubmed: 14551429doi: 10.1126/science.1089316google scholar: lookup
            12. Gillespie LK, Hoenen A, Morgan G, Mackenzie JM. The endoplasmic reticulum provides the membrane platform for biogenesis of the flavivirus replication complex.. J Virol 2010 Oct;84(20):10438-47.
              pmc: PMC2950591pubmed: 20686019doi: 10.1128/JVI.00986-10google scholar: lookup
            13. Mackenzie JM, Westaway EG. Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively.. J Virol 2001 Nov;75(22):10787-99.
              pmc: PMC114660pubmed: 11602720doi: 10.1128/JVI.75.22.10787-10799.2001google scholar: lookup
            14. Yu IM, Zhang W, Holdaway HA, Li L, Kostyuchenko VA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J. Structure of the immature dengue virus at low pH primes proteolytic maturation.. Science 2008 Mar 28;319(5871):1834-7.
              pubmed: 18369148doi: 10.1126/science.1153264google scholar: lookup
            15. Li L, Lok SM, Yu IM, Zhang Y, Kuhn RJ, Chen J, Rossmann MG. The flavivirus precursor membrane-envelope protein complex: structure and maturation.. Science 2008 Mar 28;319(5871):1830-4.
              pubmed: 18369147doi: 10.1126/science.1153263google scholar: lookup
            16. Zhang Y, Kaufmann B, Chipman PR, Kuhn RJ, Rossmann MG. Structure of immature West Nile virus.. J Virol 2007 Jun;81(11):6141-5.
              pmc: PMC1900247pubmed: 17376919doi: 10.1128/JVI.00037-07google scholar: lookup
            17. Mukherjee S, Lin TY, Dowd KA, Manhart CJ, Pierson TC. The infectivity of prM-containing partially mature West Nile virus does not require the activity of cellular furin-like proteases.. J Virol 2011 Nov;85(22):12067-72.
              pmc: PMC3209279pubmed: 21880759doi: 10.1128/JVI.05559-11google scholar: lookup
            18. Nelson S, Jost CA, Xu Q, Ess J, Martin JE, Oliphant T, Whitehead SS, Durbin AP, Graham BS, Diamond MS, Pierson TC. Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization.. PLoS Pathog 2008 May 9;4(5):e1000060.
              pmc: PMC2330159pubmed: 18464894doi: 10.1371/journal.ppat.1000060google scholar: lookup
            19. Plevka P, Battisti AJ, Junjhon J, Winkler DC, Holdaway HA, Keelapang P, Sittisombut N, Kuhn RJ, Steven AC, Rossmann MG. Maturation of flaviviruses starts from one or more icosahedrally independent nucleation centres.. EMBO Rep 2011 Jun;12(6):602-6.
              pmc: PMC3128282pubmed: 21566648doi: 10.1038/embor.2011.75google scholar: lookup
            20. Cherrier MV, Kaufmann B, Nybakken GE, Lok SM, Warren JT, Chen BR, Nelson CA, Kostyuchenko VA, Holdaway HA, Chipman PR, Kuhn RJ, Diamond MS, Rossmann MG, Fremont DH. Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody.. EMBO J 2009 Oct 21;28(20):3269-76.
              pmc: PMC2771083pubmed: 19713934doi: 10.1038/emboj.2009.245google scholar: lookup
            21. Colpitts TM, Rodenhuis-Zybert I, Moesker B, Wang P, Fikrig E, Smit JM. prM-antibody renders immature West Nile virus infectious in vivo.. J Gen Virol 2011 Oct;92(Pt 10):2281-2285.
              pmc: PMC3347797pubmed: 21697345doi: 10.1099/vir.0.031427-0google scholar: lookup
            22. Rodenhuis-Zybert IA, van der Schaar HM, da Silva Voorham JM, van der Ende-Metselaar H, Lei HY, Wilschut J, Smit JM. Immature dengue virus: a veiled pathogen?. PLoS Pathog 2010 Jan;6(1):e1000718.
              pmc: PMC2798752pubmed: 20062797doi: 10.1371/journal.ppat.1000718google scholar: lookup
            23. Sánchez-San Martín C, Liu CY, Kielian M. Dealing with low pH: entry and exit of alphaviruses and flaviviruses.. Trends Microbiol 2009 Nov;17(11):514-21.
              pmc: PMC2783195pubmed: 19796949doi: 10.1016/j.tim.2009.08.002google scholar: lookup
            24. Smit JM, Moesker B, Rodenhuis-Zybert I, Wilschut J. Flavivirus cell entry and membrane fusion.. Viruses 2011 Feb;3(2):160-171.
              pmc: PMC3206597pubmed: 22049308doi: 10.3390/v3020160google scholar: lookup
            25. Kaufmann B, Rossmann MG. Molecular mechanisms involved in the early steps of flavivirus cell entry.. Microbes Infect 2011 Jan;13(1):1-9.
              pmc: PMC3014442pubmed: 20869460doi: 10.1016/j.micinf.2010.09.005google scholar: lookup
            26. Stiasny K, Fritz R, Pangerl K, Heinz FX. Molecular mechanisms of flavivirus membrane fusion.. Amino Acids 2011 Nov;41(5):1159-63.
              pubmed: 19882217doi: 10.1007/s00726-009-0370-4google scholar: lookup
            27. Vázquez-Calvo A, Saiz JC, McCullough KC, Sobrino F, Martín-Acebes MA. Acid-dependent viral entry.. Virus Res 2012 Aug;167(2):125-37.
              pubmed: 22683298doi: 10.1016/j.virusres.2012.05.024google scholar: lookup
            28. Steinhauer DA, Wharton SA, Skehel JJ, Wiley DC, Hay AJ. Amantadine selection of a mutant influenza virus containing an acid-stable hemagglutinin glycoprotein: evidence for virus-specific regulation of the pH of glycoprotein transport vesicles.. Proc Natl Acad Sci U S A 1991 Dec 15;88(24):11525-9.
              pmc: PMC53168pubmed: 1763066doi: 10.1073/pnas.88.24.11525google scholar: lookup
            29. Kielian MC, Marsh M, Helenius A. Kinetics of endosome acidification detected by mutant and wild-type Semliki Forest virus.. EMBO J 1986 Dec 1;5(12):3103-9.
              pmc: PMC1167299pubmed: 3816755doi: 10.1002/j.1460-2075.1986.tb04616.xgoogle scholar: lookup
            30. Martín-Acebes MA, Rincón V, Armas-Portela R, Mateu MG, Sobrino F. A single amino acid substitution in the capsid of foot-and-mouth disease virus can increase acid lability and confer resistance to acid-dependent uncoating inhibition.. J Virol 2010 Mar;84(6):2902-12.
              pmc: PMC2826036pubmed: 20053737doi: 10.1128/JVI.02311-09google scholar: lookup
            31. Guirakhoo F, Hunt AR, Lewis JG, Roehrig JT. Selection and partial characterization of dengue 2 virus mutants that induce fusion at elevated pH.. Virology 1993 May;194(1):219-23.
              pubmed: 8480420doi: 10.1006/viro.1993.1252google scholar: lookup
            32. Gollins SW, Porterfield JS. The uncoating and infectivity of the flavivirus West Nile on interaction with cells: effects of pH and ammonium chloride.. J Gen Virol 1986 Sep;67 ( Pt 9):1941-50.
              pubmed: 3746254doi: 10.1099/0022-1317-67-9-1941google scholar: lookup
            33. Krishnan MN, Sukumaran B, Pal U, Agaisse H, Murray JL, Hodge TW, Fikrig E. Rab 5 is required for the cellular entry of dengue and West Nile viruses.. J Virol 2007 May;81(9):4881-5.
              pmc: PMC1900185pubmed: 17301152doi: 10.1128/JVI.02210-06google scholar: lookup
            34. Maier CC, Delagrave S, Zhang ZX, Brown N, Monath TP, Pugachev KV, Guirakhoo F. A single M protein mutation affects the acid inactivation threshold and growth kinetics of a chimeric flavivirus.. Virology 2007 Jun 5;362(2):468-74.
              pubmed: 17303204doi: 10.1016/j.virol.2007.01.008google scholar: lookup
            35. Martín-Acebes MA, Saiz JC. A West Nile virus mutant with increased resistance to acid-induced inactivation.. J Gen Virol 2011 Apr;92(Pt 4):831-40.
              pubmed: 21228127doi: 10.1099/vir.0.027185-0google scholar: lookup
            36. Córdoba L, Escribano-Romero E, Garmendia A, Saiz JC. Pregnancy increases the risk of mortality in West Nile virus-infected mice.. J Gen Virol 2007 Feb;88(Pt 2):476-480.
              pubmed: 17251565doi: 10.1099/vir.0.82439-0google scholar: lookup
            37. Garten W, Hallenberger S, Ortmann D, Schäfer W, Vey M, Angliker H, Shaw E, Klenk HD. Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones.. Biochimie 1994;76(3-4):217-25.
              pubmed: 7819326doi: 10.1016/0300-9084(94)90149-xgoogle scholar: lookup
            38. Martín-Acebes MA, Blázquez AB, Jiménez de Oya N, Escribano-Romero E, Saiz JC. West Nile virus replication requires fatty acid synthesis but is independent on phosphatidylinositol-4-phosphate lipids.. PLoS One 2011;6(9):e24970.
              pmc: PMC3176790pubmed: 21949814doi: 10.1371/journal.pone.0024970google scholar: lookup
            39. Yu IM, Holdaway HA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J. Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion.. J Virol 2009 Dec;83(23):12101-7.
              pmc: PMC2786737pubmed: 19759134doi: 10.1128/JVI.01637-09google scholar: lookup
            40. Blázquez AB, Sáiz JC. West Nile virus (WNV) transmission routes in the murine model: intrauterine, by breastfeeding and after cannibal ingestion.. Virus Res 2010 Aug;151(2):240-3.
              pubmed: 20438776doi: 10.1016/j.virusres.2010.04.009google scholar: lookup
            41. Lanciotti RS, Kerst AJ, Nasci RS, Godsey MS, Mitchell CJ, Savage HM, Komar N, Panella NA, Allen BC, Volpe KE, Davis BS, Roehrig JT. Rapid detection of west nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay.. J Clin Microbiol 2000 Nov;38(11):4066-71.
              pmc: PMC87542pubmed: 11060069doi: 10.1128/JCM.38.11.4066-4071.2000google scholar: lookup
            42. Shi PY, Tilgner M, Lo MK, Kent KA, Bernard KA. Infectious cDNA clone of the epidemic west nile virus from New York City.. J Virol 2002 Jun;76(12):5847-56.
              pmc: PMC136194pubmed: 12021317doi: 10.1128/jvi.76.12.5847-5856.2002google scholar: lookup
            43. Huss M, Wieczorek H. Inhibitors of V-ATPases: old and new players.. J Exp Biol 2009 Feb;212(Pt 3):341-6.
              pubmed: 19151208doi: 10.1242/jeb.024067google scholar: lookup
            44. Thompson BS, Moesker B, Smit JM, Wilschut J, Diamond MS, Fremont DH. A therapeutic antibody against west nile virus neutralizes infection by blocking fusion within endosomes.. PLoS Pathog 2009 May;5(5):e1000453.
              pmc: PMC2679195pubmed: 19478866doi: 10.1371/journal.ppat.1000453google scholar: lookup
            45. Ivanyi-Nagy R, Lavergne JP, Gabus C, Ficheux D, Darlix JL. RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae.. Nucleic Acids Res 2008 Feb;36(3):712-25.
              pmc: PMC2241907pubmed: 18033802doi: 10.1093/nar/gkm1051google scholar: lookup
            46. Alonso-Padilla J, de Oya NJ, Blázquez AB, Escribano-Romero E, Escribano JM, Saiz JC. Recombinant West Nile virus envelope protein E and domain III expressed in insect larvae protects mice against West Nile disease.. Vaccine 2011 Feb 17;29(9):1830-5.
              pubmed: 21211580doi: 10.1016/j.vaccine.2010.12.081google scholar: lookup
            47. Diamond MS, Shrestha B, Marri A, Mahan D, Engle M. B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus.. J Virol 2003 Feb;77(4):2578-86.
              pmc: PMC141119pubmed: 12551996doi: 10.1128/jvi.77.4.2578-2586.2003google scholar: lookup
            48. Wang Y, Lobigs M, Lee E, Müllbacher A. CD8+ T cells mediate recovery and immunopathology in West Nile virus encephalitis.. J Virol 2003 Dec;77(24):13323-34.
              pmc: PMC296062pubmed: 14645588doi: 10.1128/jvi.77.24.13323-13334.2003google scholar: lookup
            49. Hanna SL, Pierson TC, Sanchez MD, Ahmed AA, Murtadha MM, Doms RW. N-linked glycosylation of west nile virus envelope proteins influences particle assembly and infectivity.. J Virol 2005 Nov;79(21):13262-74.
              pmc: PMC1262570pubmed: 16227249doi: 10.1128/JVI.79.21.13262-13274.2005google scholar: lookup
            50. Sahenk Z, Brown A. Weak-base amines inhibit the anterograde-to-retrograde conversion of axonally transported vesicles in nerve terminals.. J Neurocytol 1991 May;20(5):365-75.
              pubmed: 1714489doi: 10.1007/BF01355533google scholar: lookup
            51. van Marle G, Antony J, Ostermann H, Dunham C, Hunt T, Halliday W, Maingat F, Urbanowski MD, Hobman T, Peeling J, Power C. West Nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence.. J Virol 2007 Oct;81(20):10933-49.
              pmc: PMC2045515pubmed: 17670819doi: 10.1128/JVI.02422-06google scholar: lookup
            52. Brault AC, Huang CY, Langevin SA, Kinney RM, Bowen RA, Ramey WN, Panella NA, Holmes EC, Powers AM, Miller BR. A single positively selected West Nile viral mutation confers increased virogenesis in American crows.. Nat Genet 2007 Sep;39(9):1162-6.
              pmc: PMC2291521pubmed: 17694056doi: 10.1038/ng2097google scholar: lookup
            53. Wicker JA, Whiteman MC, Beasley DW, Davis CT, Zhang S, Schneider BS, Higgs S, Kinney RM, Barrett AD. A single amino acid substitution in the central portion of the West Nile virus NS4B protein confers a highly attenuated phenotype in mice.. Virology 2006 Jun 5;349(2):245-53.
              pubmed: 16624366doi: 10.1016/j.virol.2006.03.007google scholar: lookup
            54. Oh W, Yang MR, Lee EW, Park KM, Pyo S, Yang JS, Lee HW, Song J. Jab1 mediates cytoplasmic localization and degradation of West Nile virus capsid protein.. J Biol Chem 2006 Oct 6;281(40):30166-74.
              pubmed: 16882664doi: 10.1074/jbc.M602651200google scholar: lookup
            55. Ivanyi-Nagy R, Darlix JL. Core protein-mediated 5'-3' annealing of the West Nile virus genomic RNA in vitro.. Virus Res 2012 Aug;167(2):226-35.
              pmc: PMC7172325pubmed: 22652509doi: 10.1016/j.virusres.2012.05.003google scholar: lookup
            56. Yang MR, Lee SR, Oh W, Lee EW, Yeh JY, Nah JJ, Joo YS, Shin J, Lee HW, Pyo S, Song J. West Nile virus capsid protein induces p53-mediated apoptosis via the sequestration of HDM2 to the nucleolus.. Cell Microbiol 2008 Jan;10(1):165-76.
              pmc: PMC7162166pubmed: 17697133doi: 10.1111/j.1462-5822.2007.01027.xgoogle scholar: lookup
            57. Medigeshi GR, Hirsch AJ, Brien JD, Uhrlaub JL, Mason PW, Wiley C, Nikolich-Zugich J, Nelson JA. West nile virus capsid degradation of claudin proteins disrupts epithelial barrier function.. J Virol 2009 Jun;83(12):6125-34.
              pmc: PMC2687390pubmed: 19369347doi: 10.1128/JVI.02617-08google scholar: lookup
            58. Oh WK, Song J. Hsp70 functions as a negative regulator of West Nile virus capsid protein through direct interaction.. Biochem Biophys Res Commun 2006 Sep 8;347(4):994-1000.
              pmc: PMC7117540pubmed: 16854374doi: 10.1016/j.bbrc.2006.06.190google scholar: lookup
            59. Hunt TA, Urbanowski MD, Kakani K, Law LM, Brinton MA, Hobman TC. Interactions between the West Nile virus capsid protein and the host cell-encoded phosphatase inhibitor, I2PP2A.. Cell Microbiol 2007 Nov;9(11):2756-66.
              pubmed: 17868381doi: 10.1111/j.1462-5822.2007.01046.xgoogle scholar: lookup
            60. Bhuvanakantham R, Chong MK, Ng ML. Specific interaction of capsid protein and importin-alpha/beta influences West Nile virus production.. Biochem Biophys Res Commun 2009 Nov 6;389(1):63-9.
              pubmed: 19712667doi: 10.1016/j.bbrc.2009.08.108google scholar: lookup
            61. Bhuvanakantham R, Li J, Tan TT, Ng ML. Human Sec3 protein is a novel transcriptional and translational repressor of flavivirus.. Cell Microbiol 2010 Apr 1;12(4):453-72.
              pubmed: 19889084doi: 10.1111/j.1462-5822.2009.01407.xgoogle scholar: lookup
            62. Ko A, Lee EW, Yeh JY, Yang MR, Oh W, Moon JS, Song J. MKRN1 induces degradation of West Nile virus capsid protein by functioning as an E3 ligase.. J Virol 2010 Jan;84(1):426-36.
              pmc: PMC2798448pubmed: 19846531doi: 10.1128/JVI.00725-09google scholar: lookup
            63. Xu Z, Anderson R, Hobman TC. The capsid-binding nucleolar helicase DDX56 is important for infectivity of West Nile virus.. J Virol 2011 Jun;85(11):5571-80.
              pmc: PMC3094978pubmed: 21411523doi: 10.1128/JVI.01933-10google scholar: lookup
            64. Dokland T, Walsh M, Mackenzie JM, Khromykh AA, Ee KH, Wang S. West Nile virus core protein; tetramer structure and ribbon formation.. Structure 2004 Jul;12(7):1157-63.
              pmc: PMC7173237pubmed: 15242592doi: 10.1016/j.str.2004.04.024google scholar: lookup
            65. Khromykh AA, Westaway EG. RNA binding properties of core protein of the flavivirus Kunjin.. Arch Virol 1996;141(3-4):685-99.
              pmc: PMC7086803pubmed: 8645104doi: 10.1007/BF01718326google scholar: lookup
            66. Mukhopadhyay S, Kuhn RJ, Rossmann MG. A structural perspective of the flavivirus life cycle.. Nat Rev Microbiol 2005 Jan;3(1):13-22.
              pubmed: 15608696doi: 10.1038/nrmicro1067google scholar: lookup
            67. Sun EC, Zhao J, Yang T, Liu NH, Geng HW, Qin YL, Wang LF, Bu ZG, Yang YH, Lunt RA, Wang LF, Wu DL. Identification of a conserved JEV serocomplex B-cell epitope by screening a phage-display peptide library with a mAb generated against West Nile virus capsid protein.. Virol J 2011 Mar 6;8:100.
              pmc: PMC3060845pubmed: 21375771doi: 10.1186/1743-422X-8-100google scholar: lookup
            68. Samsa MM, Mondotte JA, Iglesias NG, Assunção-Miranda I, Barbosa-Lima G, Da Poian AT, Bozza PT, Gamarnik AV. Dengue virus capsid protein usurps lipid droplets for viral particle formation.. PLoS Pathog 2009 Oct;5(10):e1000632.
              pmc: PMC2760139pubmed: 19851456doi: 10.1371/journal.ppat.1000632google scholar: lookup
            69. Samsa MM, Mondotte JA, Caramelo JJ, Gamarnik AV. Uncoupling cis-Acting RNA elements from coding sequences revealed a requirement of the N-terminal region of dengue virus capsid protein in virus particle formation.. J Virol 2012 Jan;86(2):1046-58.
              pmc: PMC3255831pubmed: 22072762doi: 10.1128/JVI.05431-11google scholar: lookup
            70. Kimura T, Ohyama A. Association between the pH-dependent conformational change of West Nile flavivirus E protein and virus-mediated membrane fusion.. J Gen Virol 1988 Jun;69 ( Pt 6):1247-54.
              pubmed: 3385406doi: 10.1099/0022-1317-69-6-1247google scholar: lookup
            71. Moesker B, Rodenhuis-Zybert IA, Meijerhof T, Wilschut J, Smit JM. Characterization of the functional requirements of West Nile virus membrane fusion.. J Gen Virol 2010 Feb;91(Pt 2):389-93.
              pubmed: 19828760doi: 10.1099/vir.0.015255-0google scholar: lookup
            72. Guirakhoo F, Bolin RA, Roehrig JT. The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein.. Virology 1992 Dec;191(2):921-31.
              pmc: PMC7130970pubmed: 1280384doi: 10.1016/0042-6822(92)90267-sgoogle scholar: lookup
            73. Kaufmann B, Chipman PR, Holdaway HA, Johnson S, Fremont DH, Kuhn RJ, Diamond MS, Rossmann MG. Capturing a flavivirus pre-fusion intermediate.. PLoS Pathog 2009 Nov;5(11):e1000672.
              pmc: PMC2776511pubmed: 19956725doi: 10.1371/journal.ppat.1000672google scholar: lookup
            74. Doms RW, Gething MJ, Henneberry J, White J, Helenius A. Variant influenza virus hemagglutinin that induces fusion at elevated pH.. J Virol 1986 Feb;57(2):603-13.
              pmc: PMC252775pubmed: 3003392doi: 10.1128/JVI.57.2.603-613.1986google scholar: lookup
            75. Davis CW, Nguyen HY, Hanna SL, Sánchez MD, Doms RW, Pierson TC. West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection.. J Virol 2006 Feb;80(3):1290-301.
              pmc: PMC1346927pubmed: 16415006doi: 10.1128/JVI.80.3.1290-1301.2006google scholar: lookup
            76. Jose J, Przybyla L, Edwards TJ, Perera R, Burgner JW 2nd, Kuhn RJ. Interactions of the cytoplasmic domain of Sindbis virus E2 with nucleocapsid cores promote alphavirus budding.. J Virol 2012 Mar;86(5):2585-99.
              pmc: PMC3302261pubmed: 22190727doi: 10.1128/JVI.05860-11google scholar: lookup
            77. Lopez S, Yao JS, Kuhn RJ, Strauss EG, Strauss JH. Nucleocapsid-glycoprotein interactions required for assembly of alphaviruses.. J Virol 1994 Mar;68(3):1316-23.
              pmc: PMC236585pubmed: 7508993doi: 10.1128/JVI.68.3.1316-1323.1994google scholar: lookup
            78. Snyder AJ, Sokoloski KJ, Mukhopadhyay S. Mutating conserved cysteines in the alphavirus e2 glycoprotein causes virus-specific assembly defects.. J Virol 2012 Mar;86(6):3100-11.
              pmc: PMC3302346pubmed: 22238319doi: 10.1128/JVI.06615-11google scholar: lookup
            79. Haag L, Garoff H, Xing L, Hammar L, Kan ST, Cheng RH. Acid-induced movements in the glycoprotein shell of an alphavirus turn the spikes into membrane fusion mode.. EMBO J 2002 Sep 2;21(17):4402-10.
              pmc: PMC126182pubmed: 12198142doi: 10.1093/emboj/cdf442google scholar: lookup
            80. Zhang Y, Corver J, Chipman PR, Zhang W, Pletnev SV, Sedlak D, Baker TS, Strauss JH, Kuhn RJ, Rossmann MG. Structures of immature flavivirus particles.. EMBO J 2003 Jun 2;22(11):2604-13.
              pmc: PMC156766pubmed: 12773377doi: 10.1093/emboj/cdg270google scholar: lookup
            81. Youn S, Li T, McCune BT, Edeling MA, Fremont DH, Cristea IM, Diamond MS. Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus.. J Virol 2012 Jul;86(13):7360-71.
              pmc: PMC3416313pubmed: 22553322doi: 10.1128/JVI.00157-12google scholar: lookup
            82. Nybakken GE, Nelson CA, Chen BR, Diamond MS, Fremont DH. Crystal structure of the West Nile virus envelope glycoprotein.. J Virol 2006 Dec;80(23):11467-74.
              pmc: PMC1642602pubmed: 16987985doi: 10.1128/JVI.01125-06google scholar: lookup
            83. Xue B, Dunbrack RL, Williams RW, Dunker AK, Uversky VN. PONDR-FIT: a meta-predictor of intrinsically disordered amino acids.. Biochim Biophys Acta 2010 Apr;1804(4):996-1010.
              pmc: PMC2882806pubmed: 20100603doi: 10.1016/j.bbapap.2010.01.011google scholar: lookup
            84. Krogh A, Larsson B, von Heijne G, Sonnhammer EL. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.. J Mol Biol 2001 Jan 19;305(3):567-80.
              pubmed: 11152613doi: 10.1006/jmbi.2000.4315google scholar: lookup
            85. Di Tommaso P, Moretti S, Xenarios I, Orobitg M, Montanyola A, Chang JM, Taly JF, Notredame C. T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension.. Nucleic Acids Res 2011 Jul;39(Web Server issue):W13-7.
              pmc: PMC3125728pubmed: 21558174doi: 10.1093/nar/gkr245google scholar: lookup

            Citations

            This article has been cited 10 times.
            1. Dadhich R, Kapoor S. Various Facets of Pathogenic Lipids in Infectious Diseases: Exploring Virulent Lipid-Host Interactome and Their Druggability. J Membr Biol 2020 Oct;253(5):399-423.
              doi: 10.1007/s00232-020-00135-0pubmed: 32833058google scholar: lookup
            2. Jiménez de Oya N, Escribano-Romero E, Camacho MC, Blazquez AB, Martín-Acebes MA, Höfle U, Saiz JC. A Recombinant Subviral Particle-Based Vaccine Protects Magpie (Pica pica) Against West Nile Virus Infection. Front Microbiol 2019;10:1133.
              doi: 10.3389/fmicb.2019.01133pubmed: 31231320google scholar: lookup
            3. Vázquez-Calvo Á, Jiménez de Oya N, Martín-Acebes MA, Garcia-Moruno E, Saiz JC. Antiviral Properties of the Natural Polyphenols Delphinidin and Epigallocatechin Gallate against the Flaviviruses West Nile Virus, Zika Virus, and Dengue Virus. Front Microbiol 2017;8:1314.
              doi: 10.3389/fmicb.2017.01314pubmed: 28744282google scholar: lookup
            4. Zhong R, Xin R, Chen Z, Liang N, Liu Y, Ma S, Liu X. The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death. Int J Mol Sci 2016 Nov 21;17(11).
              doi: 10.3390/ijms17111939pubmed: 27879648google scholar: lookup
            5. Blázquez AB, Martín-Acebes MA, Saiz JC. Inhibition of West Nile Virus Multiplication in Cell Culture by Anti-Parkinsonian Drugs. Front Microbiol 2016;7:296.
              doi: 10.3389/fmicb.2016.00296pubmed: 27014219google scholar: lookup
            6. Blázquez AB, Martín-Acebes MA, Saiz JC. Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response. Front Microbiol 2014;5:797.
              doi: 10.3389/fmicb.2014.00797pubmed: 25642225google scholar: lookup
            7. Aubry F, Nougairède A, Gould EA, de Lamballerie X. Flavivirus reverse genetic systems, construction techniques and applications: a historical perspective. Antiviral Res 2015 Feb;114:67-85.
              doi: 10.1016/j.antiviral.2014.12.007pubmed: 25512228google scholar: lookup
            8. Merino-Ramos T, Blázquez AB, Escribano-Romero E, Cañas-Arranz R, Sobrino F, Saiz JC, Martín-Acebes MA. Protection of a single dose west nile virus recombinant subviral particle vaccine against lineage 1 or 2 strains and analysis of the cross-reactivity with Usutu virus. PLoS One 2014;9(9):e108056.
              doi: 10.1371/journal.pone.0108056pubmed: 25229345google scholar: lookup
            9. Balinsky CA, Schmeisser H, Ganesan S, Singh K, Pierson TC, Zoon KC. Nucleolin interacts with the dengue virus capsid protein and plays a role in formation of infectious virus particles. J Virol 2013 Dec;87(24):13094-106.
              doi: 10.1128/JVI.00704-13pubmed: 24027323google scholar: lookup
            10. Dawurung JS, Harrison JJ, Modhiran N, Hall RA, Hobson-Peters J, de Malmanche H. Serum-Free Suspension Culture of the Aedes albopictus C6/36 Cell Line for Chimeric Orthoflavivirus Vaccine Production. Viruses 2025 Feb 12;17(2).
              doi: 10.3390/v17020250pubmed: 40007005google scholar: lookup
            Subscribe to our newsletter
            Join 99,030 horse owners like you who receive our email updates on horse health and nutrition.