Alphavirus antiviral drug development: Scientific gap analysis and prospective research areas

Biosecurity and Bioterrorism

Volumn 7, Issue 4, 2009, Pages 413-427

  Reichert, Erin ^a   Clase, Amanda ^b   Bacetty, Ada ^a   Larsen, Joseph ^a  

^a DEFENSE THREAT REDUCTION AGENCY   (United States)

^b Bull and Associates   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT;

ALPHA VIRUS; ARTICLE; DRUG DEVELOPMENT; DRUG EFFECT; HUMAN; LEGAL ASPECT; METHODOLOGY; ORGANIZATION AND MANAGEMENT; RESEARCH;

ALPHAVIRUS; ANTIVIRAL AGENTS; DRUG DISCOVERY; HUMANS; RESEARCH;

ALPHAVIRUS; EASTERN EQUINE ENCEPHALITIS VIRUS; VENEZUELAN EQUINE ENCEPHALITIS VIRUS; WESTERN EQUINE ENCEPHALOMYELITIS VIRUS;

EID: 77749283581     PISSN: 15387135     EISSN: None     Source Type: Journal    
DOI: 10.1089/bsp.2009.0032     Document Type: Article

References (125)

1. Richmond JY, McKinney RW. Biosafety in the Microbiological and Biomedical Laboratories. 3rd ed. Washington, DC: U.S. Department of Health & Human Services; 1994.
2. Casals J, Curnen E, Thomas L. Venezuelan equine en-cephalomyelitis in man. J Exp Med 1943;77:521-530.
3. Dietz WH, Peralta PH, Johnson KM. Ten clinical cases of human infection with Venezuelan equine encephalomyelitis virus, subtype I-D. Am J Trop Med Hyg 1979;28:329-334.
4. Lennette EH, Koprowski H. Human infection with Venezuelan equine encephalomyelitis virus: a report on eight cases of infection acquired in the laboratory. JAMA 1943;123: 1088-1095.
5. Howitt B. Recovery of the virus of equine encephalomy-elitis from the brain of a child. Science 1938;88:455-456.
6. Howitt B. Recovery of the virus of equine encephalomy-elitis (western type) from human blood serum. Science 1939;89:541-542.
7. Webster LT, Wright FH. Recovery of eastern equine encephalomyelitis virus from brain tissue of human cases of encephalitis in Massachusetts. Science 1938;88:305-306.
8. Frolov I, Schlesinger S. Comparison of the effects of Sindbis virus and Sindbis virus replicons on host cell protein synthesis and cytopathogenicity in BHK cells. J Virol 1994;68:1721-1727.
9. Ludwig GV, Turell MJ, Vogel P, et al. Comparative neu-rovirulence of attenuated and non-attenuated strains of Venezuelan equine encephalitis virus in mice. Am J Trop Med Hyg 2001;64:49-55.
10. Davis NL, Willis LV, Smith JF, Johnston RE. In vitro synthesis of infectious Venezuelan equine encephalitis virus RNA from cDNA clone: analysis of a variable deletion mutant. Virology 1989;171:189-204.
11. Davis NL, Powell N, Greenwald GF, et al. Attenuating mutations in the E2 glycoprotein gene of Venezuelan equine encpehalitis virus: construction of single and multiple mutants in a full-length cDNA clone. Virology 1991;183: 20-31.
12. Demucha Macias J, S'Anchez Spindola I. Two human cases of laboratory infection with mucambo virus. Am J Trop Med Hyg 1965;14:475-478.
13. Chairman of the Joint Chiefs of Staff. Joint Strategy for Biological Warfare Defense. Washington, DC. 2006.
14. Convention on the Prohibition of the Development, Production, and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on Their Destruction. April 10, 1972. http://www.fas.org/nuke/control/bwc/text/bwc.ht. Accessed October 22, 2009.
15. Benarroch D, Egloff MP, Mulard L, Guerreiro C, Romette JL, Canard B. A structural basis for the inhibition of the NS5 dengue virus mRNA 2′-O-methyltransferase domain by ribavirin 5′-triphosphate. J Biol Chem 2004;279: 35638-35643.
16. Borowski P, Lang M, Niebuhr A, et al. Inhibition of the helicase activity of HCV NTPase/helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide- 5′-triphosphate (ribavirin-TP). Acta Biochim Pol 2001;48:739-744.
17. Choi HK, Tong L, Minor W, et al. Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virion. Nature 1991; 354:37-43.
18. Dhanak D, Duffy KJ, Johnston VK, et al. Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Biol Chem 2002;277:38322-38327.
19. Ding MX, Schlesinger MJ. Evidence that Sindbis virus NSP2 is an autoprotease which processes the virus non-structural polyprotein. Virology 1989;171:280-284.
20. Kleymann G, Fischer R, Betz UA, et al. New helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. Nat Med 2002;8:392-398.
21. Lamarre D, Anderson PC, Bailey M, et al. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 2003;426:186-189.
22. 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;68: 5781-5791.
23. Luzhkov VB, Selisko B, Nordqvist A, et al. Virtual screening and bioassay study of novel inhibitors for dengue virus mRNA cap (nucleoside-2′O)- methyltransferase. Bioorg Med Chem 2007;15:7795-7802.
24. Melancon P, Garoff H. Processing of the Semliki Forest virus structural polyprotein: role of the capsid protease. J Virol 1987;61:1301-1309.
25. Rikkonen M, Peranen J, Kääriäinen L. ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2. J Virol 1994;68:5804-5810.
26. Shirako Y, Strauss EG, Strauss JH. Suppressor mutations that allow sindbis virus RNA polymerase to function with nonaromatic amino acids at the N-terminus: evidence for interaction between nsP1 and nsP4 in minus-strand RNA synthesis. Virology 2000;276:148-160.
27. Vasiljeva L, Merits A, Auvinen P, Kääriäinen L. Identification of a novel function of the alphavirus capping apparatus. RNA 5′-triphosphatase activity of Nsp2. J Biol Chem 2000;275:17281-17287.
28. Zhang N, Chen HM, Koch V, et al. Potent inhibition of NTPase/helicase of the West Nile Virus by ring-expanded ("fat") nucleoside analogues. J Med Chem 2003;46: 4776-4789.
29. Mueller NH, Pattabiraman N, Ansarah-Sobrinho C, Viswanathan P, Pierson TC, Padmanabhan R. Identification and biochemical characterization of small-molecule inhibitors of West Nile virus serine protease by a high-throughput screen. Antimicrob Agents Chemother 2008;52: 3385-3393.
30. Sawicki DL, Sawicki SG, Keranen S, Kääriäinen L. Specific Sindbis virus-coded function for minus-strand RNA synthesis. J Virol 1981;39:348-358.
31. Lulla V, Sawicki DL, Sawicki SG, Lulla A, Merits A, Ahola T. Molecular defects caused by temperature-sensitive mutations in Semliki forest virus nsP1. J Virol 2008;82: 9236-9244.
32. Spuul P, Salonen A, Merits A, Jokitalo E, Kääriäinen L, Ahola T. Role of the amphipathic peptide of Semliki forest virus replicase protein nsP1 in membrane association and virus replication. J Virol 2007;81:872-883.
33. Ahola T, Kääriäinen L. Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci USA 1995;92:507-511.
34. Laakkonen P, Hyvonen M, Peranen J, Kääriäinen L. Expression of Semliki forest virus nsP1-specific methyl-transferase in insect cells and in Escherichia coli. J Virol 1994;68:7418-7425.
35. Mi S, Stollar V. Expression of Sindbis virus nsP1 and methyltransferase activity in Escherichia coli. Virology 1991; 184:423-427.
36. Rozanov MN, Koonin EV, Gorbalenya AE. Conservation of the putative methyltransferase domain: a hallmark of the 'Sindbis-like' supergroup of positive-strand RNA viruses. J Gen Virol 1992;73:2129-2134.
37. Lim SP, Wen D, Yap TL, Yan CK, Lescar J, Vasudevan SG. A scintillation proximity assay for dengue virus NS5 2′-O-methyltransferase-kinetic and inhibition analyses. Antiviral Res 2008;80:360-369.
38. Lampio A, Ahola T, Darzynkiewicz E, Stepinski J, Jankowska-Anyszka M, Kaariainen L. Guanosine analogs as inhibitors of alphavirus mRNA capping enzyme. Antiviral Res 1999;42:35-46.
39. Suopanki J, Sawicki DL, Sawicki SG, Kääriäinen L. Regulation of alphavirus 26S mRNA transcription by replicase component nsP2. J Gen Virol 1998;79:309-319.
40. Balistreri G, Caldentey J, Kääriäinen L, Ahola T. Enzymatic defects of the nsP2 proteins of Semliki Forest virus temperature-sensitive mutants. J Virol 2007;81:2849-2860.
41. Peranen J, Rikkonen M, Liljestrom P, Kääriäinen L. Nuclear localization of Semliki Forest virus-specific nonstruc-tural protein nsP2. J Virol 1990;64:1888-1896.
42. Sawicki DL, Sawicki SG. A second nonstructural protein functions in the regulation of alphavirus negative-strand RNA synthesis. J Virol 1993;67:3605-3610.
43. Merits A, Vasiljeva L, Ahola T, Kääriäinen L, Auvinen P. Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease. J Gen Virol 2001; 82:765-773.
44. Zhang D, Tozser J, Waugh DS. Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses. Protein Expr Purif 2009;64:89-97.
45. Aliperti G, Schlesinger MJ. Evidence for an autoprotease activity of sindbis virus capsid protein. Virology 1978;90: 366-369.
46. Lin TI, Lenz O, Fanning G, et al. In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor. Antimicrob Agents Chemother 2009;53:1377-1385.
47. Mederacke I, Wedemeyer H, Manns MP. Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. Curr Opin Investig Drugs 2009;10:181-189.
48. Russo AT, White MA, Watowich SJ. The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease. Structure 2006;14:1449-1458.
49. Gomez de Cedron M, Ehsani N, Mikkola ML, Garcia JA, Kääriä inen L. RNA helicase activity of Semliki Forest virus replicase protein NSP2. FEBS Lett 1999;448:19-22.
50. Biswas S, Jennens L, Field HJ. The helicase primase inhibitor, BAY 57-1293 shows potent therapeutic antiviral activity superior to famciclovir in BALB/c mice infected with herpes simplex virus type 1. Antiviral Res 2007;75: 30-35.
51. Gozedek A, Zhukov I, Polkowska A, et al. NS3 Peptide, a novel potent hepatitis C virus NS3 helicase inhibitor: its mechanism of action and antiviral activity in the replicon system. Antimicrob Agents Chemother 2008;52:393-401.
52. Vihinen H, Ahola T, Tuittila M, Merits A, Kääriäinen L. Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3. J Biol Chem 2001;276:5745-5752.
53. De I, Fata-Hartley C, Sawicki SG, Sawicki DL. Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus. J Virol 2003;77:13106-13116.
54. Wang YF, Sawicki SG, Sawicki DL. Alphavirus nsP3 functions to form replication complexes transcribing negative-strand RNA. J Virol 1994;68:6466-6475.
55. Gorchakov R, Garmashova N, Frolova E, Frolov I. Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 2008;82:10088-10101.
56. Rubach JK, Wasik BR, Rupp JC, Kuhn RJ, Hardy RW, Smith JL. Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro. Virology 2009;384:201-208.
57. Thal MA, Wasik BR, Posto J, Hardy RW. Template requirements for recognition and copying by Sindbis virus RNA-dependent RNA polymerase. Virology 2007;358: 221-232.
58. de Groot RJ, Rumenapf T, Kuhn RJ, Strauss EG, Strauss JH. Sindbis virus RNA polymerase is degraded by the N-end rule pathway. Proc Natl Acad Sci USA 1991;88: 8967-8971.
59. Tomar S, Hardy RW, Smith JL, Kuhn RJ. Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity. J Virol 2006;80:9962-9969.
60. Koch U, Narjes F. Recent progress in the development of inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. Curr Top Med Chem 2007;7:1302-1329.
61. Soriano V, Peters MG, Zeuzem S. New therapies for hepatitis C virus infection. Clin Infect Dis 2009;48:313-320.
62. Kim HY, Patkar C, Warrier R, Kuhn R, Cushman M. Design, synthesis, and evaluation of dioxane-based antiviral agents targeted against the Sindbis virus capsid protein. Bioorg Med Chem Lett 2005;15:3207-3211.
63. Elgizoli M, Dai Y, Kempf C, Koblet H, Michel MR. Semliki Forest virus capsid protein acts as a pleiotropic regulator of host cellular protein synthesis. J Virol 1989;63: 2921-2928.
64. Frolova EI, Fayzulin RZ, Cook SH, Griffin DE, Rice CM, Frolov I. Roles of nonstructural protein nsP2 and Alpha/Beta interferons in determining the outcome of Sindbis virus infection. J Virol 2002;76:11254-11264.
65. Joe AK, Foo HH, Kleeman L, Levine B. The transmem-brane domains of Sindbis virus envelope glycoproteins induce cell death. J Virol 1998;72:3935-3943.
66. Johnston C, Jiang W, Chu T, Levine B. Identification of genes involved in the host response to neurovirulent al-phavirus infection. J Virol 2001;75:10431-10445.
67. Levine B, Griffin DE. Molecular analysis of neurovirulent strains of Sindbis virus that evolve during persistent infection of scid mice. J Virol 1993;67:6872-6875.
68. Scallan MF, Allsopp TE, Fazakerley JK. bcl-2 acts early to restrict Semliki Forest virus replication and delays virus-induced programmed cell death. J Virol 1997;71:1583-1590.
69. van Steeg H, Kasperaitis M, Voorma HO, Benne R. Infection of neuroblastoma cells by Semliki Forest virus. The interference of viral capsid protein with the binding of host messenger RNAs into initiation complexes is the cause of the shut-off of host protein synthesis. Eur J Biochem 1984;138:473-478.
70. Zhang X, Qu J, Ding M, Ren X, Qiu Y. The mutiplication of Sindbis virus and host BHK-21 cell apoptosis. Wei Sheng Wu Xue Bao 1997;37:165-170.
71. Montgomery SA, Johnston RE. Nuclear import and export of Venezuelan equine encephalitis virus nonstructural protein 2. J Virol 2007;81:10268-10279.
72. 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;81:13552-13565.
73. Favre D, Studer E, Michel MR. Two nucleolar targeting signals present in the N-terminal part of Semliki Forest virus capsid protein. Arch Virol 1994;137:149-155.
74. Garmashova N, Gorchakov R, Frolova E, Frolov I. Sindbis virus nonstructural protein nsP2 is cytotoxic and inhibits cellular transcription. J Virol 2006;80:5686-5696.
75. Aguilar PV, Weaver SC, Basler CF. Capsid protein of eastern equine encephalitis virus inhibits host cell gene expression. J Virol 2007;81:3866-3876.
76. Garmashova N, Gorchakov R, Volkova E, Paessler S, Frolova E, Frolov I. The Old World and New World al-phaviruses use different virus-specific proteins for induction of transcriptional shutoff. J Virol 2007;81:2472-2484.
77. Atasheva S, Garmashova N, Frolov I, Frolova E. Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in mammalian but not in mosquito cells. J Virol 2008;82:4028-4041.
78. Jan JT, Chatterjee S, Griffin DE. Sindbis virus entry into cells triggers apoptosis by activating sphingomyelinase, leading to the release of ceramide. J Virol 2000;74:6425-6432.
79. Levine B, Golaman JE, Jiang HH, Griffin DE, Hardwick JM. Bcl-2 protects mice against lethal alphavirus encephalitis. Proc Natl Acad Sci USA 1996;93:4810-4815.
80. Liang XH, Kleeman LK, Jiang HH, et al. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 1998;72:8586-8596.
81. Lewis J, Oyler GA, Ueno K, et al. Inhibition of virus-induced neuronal apoptosis by Bax. Nat Med 1999;5: 832-835.
82. Breakwell L, Dosenovic P, Karlsson Hedestam GB, et al. Semliki Forest virus nonstructural protein 2 is involved in suppression of the type I interferon response. J Virol 2007; 81:8677-8684.
83. Grieder FB, Vogel SN. Role of interferon and interferon regulatory factors in early protection against Venezuelan equine encephalitis virus infection. Virology 1999;257:106-118.
84. Barry G, Breakwell L, Fragkoudis R, et al. 2009. PKR acts early in infection to suppress Semliki Forest virus production and strongly enhances the type-I interferon response. J Gen Virol 2009;90:1382-1391.
85. Ryman KD, Meier KC, Nangle EM, et al. Sindbis virus translation is inhibited by a PKR/RNase L-independent effector induced by alpha/beta interferon priming of dendritic cells. J Virol 2005;79:1487-1499.
86. Lenschow DJ, Giannakopoulos NV, Gunn LJ, et al. Identifcation of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol 2005;79:13974-13983.
87. Lenschow DJ, Lai C, Frias-Staheli N, et al. IFN-stimulated gene 15 functions as a critical antiviral molecule against influenza, herpes, and Sindbis viruses. Proc Natl Acad Sci USA 2007;104:1371-1376.
88. Labrada L, Liang XH, Zheng W, Johnston C, Levine B. Age-dependent resistance to lethal alphavirus encephalitis in mice: analysis of gene expression in the central nervous system and identification of a novel interferon-inducible protective gene, mouse ISG12. J Virol 2002;76:11688-11703.
89. Kolokoltsova OA, Domina AM, Kolokoltsov AA, Davey RA, Weaver SC, Watowich SJ. Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling. Virology 2008;377:133-142.
90. Nur-E-Kamal MS, Varga M, Maruta H. The GTPase-activating NF1 fragment of 91 amino acids reverses v-Ha-Ras-induced malignant phenotype. J Biol Chem 1993; 268:22331-22337.
91. Joe AK, Ferrari G, Jiang HH, Liang XH, Levine B. Dominant inhibitory Ras delays Sindbis virus-induced ap-optosis in neuronal cells. J Virol 1996;70:7744-7751.
92. Burdeinick-Kerr R, Griffin DE. Gamma interferon-dependent, noncytolytic clearance of sindbis virus infection from neurons in vitro. J Virol 2005;79:5374-5385.
93. Burdeinick-Kerr R, Govindarajan D, Griffin DE. Non-cytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on Jak/STAT signaling. J Virol 2009;83:3429-3435.
94. Silvestri LS, Ruthel G, Kallstrom G, et al. Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction. J Infect Dis 2007; 196(Suppl 2):S264-S270.
95. Nargi-Aizenman JL, Griffin DE. Sindbis virus-induced neuronal death is both necrotic and apoptotic and is ameliorated by N-methyl-D-aspartate receptor antagonists. J Virol 2001;75:7114-7121.
96. Nargi-Aizenman JL, Havert MB, Zhang M, Irani DN, Rothstein JD, Griffin DE. Glutamate receptor antagonists protect from virus-induced neural degeneration. Ann Neurol 2004;55:541-549.
97. Greene IP, Lee EY, Prow N, Ngwang B, Griffin DE. Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection. Proc Natl Acad Sci USA 2008;105: 3575-3580.
98. Irani DN, Prow NA. Neuroprotective interventions targeting detrimental host immune responses protect mice from fatal alphavirus encephalitis. J Neuropathol Exp Neurol 2007;66:533-544.
99. Prow NA, Irani DN. The opioid receptor antagonist, nal-oxone, protects spinal motor neurons in a murine model of alphavirus encephalomyelitis. Exp Neurol 2007;205:461-470.
100. Tamberg N, Lulla V, Fragkoudis R, Lulla A, Fazakerley J, Merits A. Insertion of EGFP into the replicase gene of Semliki Forest virus results in a novel, genetically stable marker virus. J Gen Virol 2007;88:1225-1230.
101. U.S. Centers for Disease Control and Prevention. Information on Arboviral Encephalitides. November 7, 2005. http://www.cdc.gov/ncidod/dvbid/Arbor/arbdet. htm. Accessed October 22, 2009.
102. Bowen GS, Fashinell TR, Dean PB, Gregg MB. Clinical aspects of human Venezuelan equine encephalitis in Texas. Bull Pan Am Health Organ 1976;10:46-57.
103. Hanson RP, Sulkin SE, Beuscher EL, Hammon WM, McKinney RW, Work TH. Arbovirus infections of laboratory workers. Extent of problem emphasizes the need for more effective measures to reduce hazards. Science 1967;158:1283-1286.
104. Fothergill LD, Holden M, Wyckoff RWG. Western equine encephalomyelitis in a laboratory worker. JAMA 1939;113: 206-207.
105. Gold H, Hampil B. Equine encephalomyelitis in a laboratory technician with recovery. Ann Intern Med 1942;16: 556-559.
106. Helwig FC. Western equine encephalomyelitis following accidental inoculation with chick embryo virus. JAMA 1940;115:291-292.
107. U.S. Food and Drug Administration. New drug and biological drug products: evidence needed to demonstrate effectiveness of new drugs when human efficacy studies are not ethical or feasible. Fed Regist 2002;67:37988-37998.
108. Calisher CH, Maness KC. Virulence of Venezuelan equine encephalomyelitis virus subtypes for various laboratory hosts. Appl Microbiol 1974;28:881-884.
109. Charles PC, Walters E, Margolis F, Johnston RE. Mechanism of neuroinvasion of Venezuelan equine encephalitis virus in the mouse. Virology 1995;208:662-671.
110. Jackson AC, SenGupta SK, Smith JF. Pathogenesis of Venezuelan equine encephalitis virus infection in mice and hamsters. Vet Pathol 1991;28:410-418.
111. Vogel P, Abplanalp D, Kell W, et al. Venezuelan equine encephalitis in BALB/c mice: kinetic analysis of central nervous system infection following aerosol or subcutaneous inoculation. Arch Pathol Lab Med 1996;120:164-172.
112. Reed DS, Lind CM, Sullivan LJ, Pratt WD, Parker MD. Aerosol infection of cynomolgus macaques with enzootic strains of Venezuelan equine encephalitis viruses. J Infect Dis 2004;189:1013-1017.
113. Ryzhikov AB, Ryabchikova EI, Sergeev AN, Tkacheva NV. Spread of Venezuelan equine encephalitis virus in mice olfactory tract. Arch Virol 1995;140:2243-2254.
114. Danes L, Kufner J, Hrusková J, Rychterová V. The role of the olfactory route on infection of the respiratory tract with Venezuelan equine encephalomyelitis virus in normal and operated Macaca rhesus monkeys. I. Results of virological examination. Acta Virol 1973;17:50-56.
115. Steele KE, Davis KJ, Stephan K, Kell W, Vogel P, Hart MK. 1998. Comparative neurovirulence and tissue tropism of wild-type and attenuated strains of Venezuelan equine encephalitis virus administered by aerosol in C3H/HeN and BALB/c mice. Vet Pathol 1998;35:386-397.
116. Vogel P, Kell WM, Fritz DL, Parker MD, Schoepp RJ. Early events in the pathogenesis of eastern equine encephalitis virus in mice. Am J Pathol 2005;166:159-171.
117. Paessler S, Aguilar P, Anishchenko M, et al. The hamster as an animal model for eastern equine encephalitis and its use in studies of virus entrance into the brain. J Infect Dis 2004;189:2072-2076.
118. Deresiewicz RL, Thaler SJ, Hsu L, Zamani AA. Clinical and neuroradiographic manifestations of eastern equine encephalitis. N Engl J Med 1997;336:1867-1874.
119. Reed DS, Lackemeyer MG, Garza NL, et al. Severe encephalitis in cynomolgus macaques exposed to aerosolized eastern equine encephalitis virus. J Infect Dis 2007;196: 441-450.
120. Liu C, Voth DW, Rodina P, Shauf LR, Gonzalez G. A comparative study of the pathogenesis of western equine and eastern equine encephalomyelitis viral infections in mice by intracerebral and subcutaneous inoculations. J Infect Dis 1970;122:53-63.
121. Aguilar MJ. Pathological changes in brain and other target organs of infant and weanling mice after infection with non-neuroadapted western equine encephalitis virus. Infect Immun 1970;2:533-542.
122. Zlotnik I, Peacock S, Grant DP, Batter-Hatton D. The pathogenesis of western equine encephalitis virus (W.E.E.) in adult hamsters with special reference to the long and short term effects on the C.N.S. of the attenuated clone 15 variant. Br J Exp Pathol 1972;53:59-77.
123. Bianchi TI, Avilés G, Sabattini MS. Biological characteristics of an enzootic subtype of western equine en-cephalomyelitis virus from Argentina. Acta Virol 1997;41: 13-20.
124. Reed DS, Larsen T, Sullivan LJ, et al. Aerosol exposure to western equine encephalitis virus causes fever and encephalitis in cynomolgus macaques. J Infect Dis 2005;192:1173-1182.
125. Malet H, Coutard B, Jamal S, et al. The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 2009;83:6534-6545.