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Reverse Genetics Approaches to Control Arenavirus

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Vaccine Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1403))

Abstract

Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors.

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Abbreviations

αDG:

Alpha-dystroglycan

AHF:

Argentine hemorrhagic fever

ATCC:

American Type Culture Collection

BHK-21:

Baby hamster kidney cells

BSA:

Albumin bovine serum

BSL:

Biosafety level

CAT:

Chloramphenicol acetyltransferase

CD:

Codon optimization

CHPV:

Chapare virus

Cluc:

Cypridina luciferase

CPE:

Cytopathic effect

cRNA:

Complementary RNA

DMEM:

Dulbecco’s modified Eagle’s medium

DN:

Dominant negative

FBS:

Fetal bovine serum

FDA:

Food and Drug Administration

FFU:

Fluorescence forming units

Gluc:

Gaussia luciferase

GFP:

Green fluorescent protein

GOI:

Gene of interest

GP:

Glycoprotein

GTOV:

Guanarito virus

HF:

Hemorrhagic fever

HTS:

High-throughput screening

IGR:

Intergenic region

ING:

Investigational new drug

JUNV:

Junin virus

IMP:

Inosine-5′-monophosphate

L:

Large RNA segment

LASV:

Lassa virus

LCMV:

Lymphocytic choriomeningitis virus

LF:

Lassa fever

LUJV:

Lujo virus

LPF2000:

Lipofectamine 2000

MACV:

Machupo virus

MG:

Minigenome

MHC:

Major histocompatibility complex

MOI:

Multiplicity of infection

MOPV:

Mopeia virus

mRNA:

Messenger RNA

MVB:

Multivesicular endosomes

NHP:

Nonhuman primates

NW:

New World

NP:

Nucleoprotein

NS:

Negative-stranded

OCEV:

Ocozocoautla de Espinosa virus

ON:

Overnight

ORF:

Open reading frame

OW:

Old World

PBS:

Phosphate-buffered saline

pA:

Polyadenylation signal

PICV:

Pichinde virus

Pol-I:

Polymerase I

Pol-II:

Polymerase II

PS:

Penicillin/streptomycin

RdRp:

RNA-dependent RNA polymerase

Rib:

Ribavirin

RT:

Room temperature

r3:

Recombinant tri-segmented

S:

Small RNA segment

SABV:

Sabia virus

S1P:

Site-1 protease

SAH:

S-adenosylhomocysteine

siRNA:

Small interfering RNA

TCRV:

Tacaribe virus

TCS:

Tissue culture supernatants

TNF:

Tumor necrosis factor

UTR:

Untranslated regions

vRNA:

Viral RNA

VSV:

Vesicular stomatitis virus

vRNPs:

Viral ribonucleoproteins

WWAV:

Whitewater Arroyo virus

WT:

Wild-type

Z:

Matrix-like small RING finger protein

References

  1. Buchmeier MJ, de la Torre, J. C., Peters, C. J. (2007) Arenaviridae: The Viruses and Their Replication. In: David Knipe P, Peter Howley, MD, Diane Griffin, MD, PhD, Robert Lamb, PhD, ScD, Malcolm Martin, MD, Bernard Roizman, ScD, Stephen Straus, MD, editor. Fields Virology. 5th ed. Philadelphia, PA, 19106, USA: Lippincott Williams & Wilkins. pp. 1791–1827

    Google Scholar 

  2. Radoshitzky SR, Bao Y, Buchmeier MJ, Charrel RN, Clawson AN et al (2015) Past, present, and future of arenavirus taxonomy. Arch Virol 160:1851–1874

    Article  CAS  PubMed  Google Scholar 

  3. Stenglein MD, Jacobson ER, Chang LW, Sanders C, Hawkins MG et al (2015) Widespread recombination, reassortment, and transmission of unbalanced compound viral genotypes in natural arenavirus infections. PLoS Pathog 11:e1004900

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Stenglein MD, Leavitt EB, Abramovitch MA, McGuire JA, DeRisi JL (2014) Genome sequence of a Bornavirus recovered from an African Garter snake (Elapsoidea loveridgei). Genome Announc 2:e00779–e00814

    Article  PubMed  PubMed Central  Google Scholar 

  5. Stenglein MD, Sanders C, Kistler AL, Ruby JG, Franco JY et al (2012) Identification, characterization, and in vitro culture of highly divergent arenaviruses from boa constrictors and annulated tree boas: candidate etiological agents for snake inclusion body disease. MBio 3:e00180-00112

    Article  CAS  Google Scholar 

  6. Enria DA, Briggiler AM, Sanchez Z (2008) Treatment of Argentine hemorrhagic fever. Antiviral Res 78:132–139

    Article  CAS  PubMed  Google Scholar 

  7. Geisbert TW, Jahrling PB (2004) Exotic emerging viral diseases: progress and challenges. Nat Med 10:S110–S121

    Article  CAS  PubMed  Google Scholar 

  8. Khan SH, Goba A, Chu M, Roth C, Healing T et al (2008) New opportunities for field research on the pathogenesis and treatment of Lassa fever. Antiviral Res 78:103–115

    Article  CAS  PubMed  Google Scholar 

  9. McCormick JB, Fisher-Hoch SP (2002) Lassa Fever. In: Oldstone MB (ed) Arenaviruses I. Springer, Berlin, Heidelberg, New York, pp 75–110

    Chapter  Google Scholar 

  10. Peters CJ (2002) Human Infection with Arenaviruses in the Americas. In: Oldstone MB (ed) Arenaviruses I. Springer, Berlin, Heidelberg, New York, pp 65–74

    Chapter  Google Scholar 

  11. Freedman DO, Woodall J (1999) Emerging infectious diseases and risk to the traveler. Med Clin North Am 83:865–883, v

    CAS  PubMed  Google Scholar 

  12. Holmes GP, McCormick JB, Trock SC, Chase RA, Lewis SM et al (1990) Lassa fever in the United States. Investigation of a case and new guidelines for management. N Engl J Med 323:1120–1123

    Article  CAS  PubMed  Google Scholar 

  13. Isaacson M (2001) Viral hemorrhagic fever hazards for travelers in Africa. Clin Infect Dis 33:1707–1712

    Article  CAS  PubMed  Google Scholar 

  14. Richmond JK, Baglole DJ (2003) Lassa fever: epidemiology, clinical features, and social consequences. BMJ 327:1271–1275

    Article  PubMed  PubMed Central  Google Scholar 

  15. Briese T, Paweska JT, McMullan LK, Hutchison SK, Street C et al (2009) Genetic detection and characterization of Lujo virus, a new hemorrhagic fever-associated arenavirus from southern Africa. PLoS Pathog 5:e1000455

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Kuns ML (1965) Epidemiology of Machupo virus infection. II. Ecological and control studies of hemorrhagic fever. Am J Trop Med Hyg 14:813–816

    CAS  PubMed  Google Scholar 

  17. Webb PA, Johnson KM, Mackenzie RB, Kuns ML (1967) Some characteristics of Machupo virus, causative agent of Bolivian hemorrhagic fever. Am J Trop Med Hyg 16:531–538

    CAS  PubMed  Google Scholar 

  18. Delgado S, Erickson BR, Agudo R, Blair PJ, Vallejo E et al (2008) Chapare virus, a newly discovered arenavirus isolated from a fatal hemorrhagic fever case in Bolivia. PLoS Pathog 4:e1000047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Gonzalez JP, Bowen MD, Nichol ST, Rico-Hesse R (1996) Genetic characterization and phylogeny of Sabia virus, an emergent pathogen in Brazil. Virology 221:318–324

    Article  CAS  PubMed  Google Scholar 

  20. Armstrong LR, Dembry LM, Rainey PM, Russi MB, Khan AS et al (1999) Management of a Sabia virus-infected patients in a US hospital. Infect Control Hosp Epidemiol 20:176–182

    Article  CAS  PubMed  Google Scholar 

  21. Tesh RB, Jahrling PB, Salas R, Shope RE (1994) Description of Guanarito virus (Arenaviridae: Arenavirus), the etiologic agent of Venezuelan hemorrhagic fever. Am J Trop Med Hyg 50:452–459

    CAS  PubMed  Google Scholar 

  22. Weaver SC, Salas RA, de Manzione N, Fulhorst CF, Duno G et al (2000) Guanarito virus (Arenaviridae) isolates from endemic and outlying localities in Venezuela: sequence comparisons among and within strains isolated from Venezuelan hemorrhagic fever patients and rodents. Virology 266:189–195

    Article  CAS  PubMed  Google Scholar 

  23. Gonzalez JP, Sanchez A, Rico-Hesse R (1995) Molecular phylogeny of Guanarito virus, an emerging arenavirus affecting humans. Am J Trop Med Hyg 53:1–6

    CAS  PubMed  Google Scholar 

  24. Fulhorst CF, Bowen MD, Ksiazek TG, Rollin PE, Nichol ST et al (1996) Isolation and characterization of Whitewater Arroyo virus, a novel North American arenavirus. Virology 224:114–120

    Article  CAS  PubMed  Google Scholar 

  25. Charrel RN, de Lamballerie X, Fulhorst CF (2001) The Whitewater Arroyo virus: natural evidence for genetic recombination among Tacaribe serocomplex viruses (family Arenaviridae). Virology 283:161–166

    Article  CAS  PubMed  Google Scholar 

  26. Cajimat MN, Milazzo ML, Bradley RD, Fulhorst CF (2012) Ocozocoautla de espinosa virus and hemorrhagic fever, Mexico. Emerg Infect Dis 18:401–405

    Article  PubMed  PubMed Central  Google Scholar 

  27. Barton LL, Mets MB (1999) Lymphocytic choriomeningitis virus: pediatric pathogen and fetal teratogen. Pediatr Infect Dis J 18:540–541

    Article  CAS  PubMed  Google Scholar 

  28. Barton LL, Mets MB (2001) Congenital lymphocytic choriomeningitis virus infection: decade of rediscovery. Clin Infect Dis 33:370–374

    Article  CAS  PubMed  Google Scholar 

  29. Barton LL, Mets MB, Beauchamp CL (2002) Lymphocytic choriomeningitis virus: emerging fetal teratogen. Am J Obstet Gynecol 187:1715–1716

    Article  PubMed  Google Scholar 

  30. Jahrling PB, Peters CJ (1992) Lymphocytic choriomeningitis virus. A neglected pathogen of man. Arch Pathol Lab Med 116:486–488

    CAS  PubMed  Google Scholar 

  31. Mets MB, Barton LL, Khan AS, Ksiazek TG (2000) Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital chorioretinitis. Am J Ophthalmol 130:209–215

    Article  CAS  PubMed  Google Scholar 

  32. Fischer SA, Graham MB, Kuehnert MJ, Kotton CN, Srinivasan A et al (2006) Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med 354:2235–2249

    Article  CAS  PubMed  Google Scholar 

  33. Palacios G, Druce J, Du L, Tran T, Birch C et al (2008) A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 358:991–998

    Article  CAS  PubMed  Google Scholar 

  34. Peters CJ (2006) Lymphocytic choriomeningitis virus-an old enemy up to new tricks. N Engl J Med 354:2208–2211

    Article  CAS  PubMed  Google Scholar 

  35. Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM et al (2002) Hemorrhagic fever viruses as biological weapons: medical and public health management. JAMA 287:2391–2405

    Article  PubMed  Google Scholar 

  36. Damonte EB, Coto CE (2002) Treatment of arenavirus infections: from basic studies to the challenge of antiviral therapy. Adv Virus Res 58:125–155

    Article  CAS  PubMed  Google Scholar 

  37. Harvie P, Omar RF, Dusserre N, Desormeaux A, Gourde P et al (1996) Antiviral efficacy and toxicity of ribavirin in murine acquired immunodeficiency syndrome model. J Acquir Immune Defic Syndr Hum Retrovirol 12:451–461

    Article  CAS  PubMed  Google Scholar 

  38. Omar RF, Harvie P, Gourde P, Desormeaux A, Tremblay M et al (1997) Antiviral efficacy and toxicity of ribavirin and foscarnet each given alone or in combination in the murine AIDS model. Toxicol Appl Pharmacol 143:140–151

    Article  CAS  PubMed  Google Scholar 

  39. Snell NJ (2001) Ribavirin—current status of a broad spectrum antiviral agent. Expert Opin Pharmacother 2:1317–1324

    Article  CAS  PubMed  Google Scholar 

  40. Enria DA, Barrera Oro JG (2002) Junin virus vaccines. Curr Top Microbiol Immunol 263:239–261

    CAS  PubMed  Google Scholar 

  41. Maiztegui JI, McKee KT Jr, Barrera Oro JG, Harrison LH, Gibbs PH et al (1998) Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group. J Infect Dis 177:277–283

    Article  CAS  PubMed  Google Scholar 

  42. Falzarano D, Feldmann H (2013) Vaccines for viral hemorrhagic fevers—progress and shortcomings. Curr Opin Virol 3:343–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Albarino CG, Bergeron E, Erickson BR, Khristova ML, Rollin PE et al (2009) Efficient reverse genetics generation of infectious Junin viruses differing in glycoprotein processing. J Virol 83:5606–5614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Emonet SF, Seregin AV, Yun NE, Poussard AL, Walker AG et al (2011) Rescue from cloned cDNAs and in vivo characterization of recombinant pathogenic Romero and live-attenuated Candid #1 strains of Junin virus, the causative agent of Argentine hemorrhagic fever disease. J Virol 85:1473–1483

    Article  CAS  PubMed  Google Scholar 

  45. Hass M, Golnitz U, Muller S, Becker-Ziaja B, Gunther S (2004) Replicon system for Lassa virus. J Virol 78:13793–13803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Albarino CG, Bird BH, Chakrabarti AK, Dodd KA, Erickson BR et al (2011) Efficient rescue of recombinant Lassa virus reveals the influence of S segment noncoding regions on virus replication and virulence. J Virol 85:4020–4024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB et al (1986) Lassa fever. Effective therapy with ribavirin. N Engl J Med 314:20–26

    Article  CAS  PubMed  Google Scholar 

  48. Kilgore PE, Ksiazek TG, Rollin PE, Mills JN, Villagra MR et al (1997) Treatment of Bolivian hemorrhagic fever with intravenous ribavirin. Clin Infect Dis 24:718–722

    Article  CAS  PubMed  Google Scholar 

  49. McKee KT Jr, Huggins JW, Trahan CJ, Mahlandt BG (1988) Ribavirin prophylaxis and therapy for experimental argentine hemorrhagic fever. Antimicrob Agents Chemother 32:1304–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Leyssen P, De Clercq E, Neyts J (2008) Molecular strategies to inhibit the replication of RNA viruses. Antiviral Res 78:9–25

    Article  CAS  PubMed  Google Scholar 

  51. Parker WB (2005) Metabolism and antiviral activity of ribavirin. Virus Res 107:165–171

    Article  CAS  PubMed  Google Scholar 

  52. Cameron CE, Castro C (2001) The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase. Curr Opin Infect Dis 14:757–764

    Article  CAS  PubMed  Google Scholar 

  53. Crotty S, Maag D, Arnold JJ, Zhong W, Lau JYN et al (2000) The broad-spectrum antiviral ribonucleotide, ribavirin, is an RNA virus mutagen. Nat Med 6:1375–1379

    Article  CAS  PubMed  Google Scholar 

  54. Ruiz-Jarabo CM, Ly C, Domingo E, de la Torre JC (2003) Lethal mutagenesis of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). Virology 308:37–47

    Article  CAS  PubMed  Google Scholar 

  55. Hoffmann HH, Kunz A, Simon VA, Palese P, Shaw ML (2011) Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis. Proc Natl Acad Sci U S A 108:5777–5782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ortiz-Riano E, Ngo N, Devito S, Eggink D, Munger J et al (2014) Inhibition of arenavirus by A3, a pyrimidine biosynthesis inhibitor. J Virol 88:878–889

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Gowen BB, Juelich TL, Sefing EJ, Brasel T, Smith JK et al (2013) Favipiravir (T-705) inhibits Junin virus infection and reduces mortality in a guinea pig model of Argentine hemorrhagic fever. PLoS Negl Trop Dis 7:e2614

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Mendenhall M, Russell A, Juelich T, Messina EL, Smee DF et al (2011) T-705 (favipiravir) inhibition of arenavirus replication in cell culture. Antimicrob Agents Chemother 55:782–787

    Article  CAS  PubMed  Google Scholar 

  59. Bolken TC, Laquerre S, Zhang Y, Bailey TR, Pevear DC et al (2005) Identification and characterization of potent small molecule inhibitor of hemorrhagic fever New World arenaviruses. Antiviral Res 69:86–97

    Article  PubMed  CAS  Google Scholar 

  60. Lee AM, Rojek JM, Spiropoulou CF, Gundersen AT, Jin W et al (2008) Unique small molecule entry inhibitors of hemorrhagic fever arena viruses. J Biol Chem 283:18734–18742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lee KJ, Novella IS, Teng MN, Oldstone MB, de La Torre JC (2000) NP and L proteins of lymphocytic choriomeningitis virus (LCMV) are sufficient for efficient transcription and replication of LCMV genomic RNA analogs. J Virol 74:3470–3477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Strecker T, Eichler R, Meulen J, Weissenhorn W, Dieter Klenk H et al (2003) Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected]. J Virol 77:10700–10705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Perez M, Craven RC, de la Torre JC (2003) The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A 100:12978–12983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Urata S, Noda T, Kawaoka Y, Yokosawa H, Yasuda J (2006) Cellular factors required for Lassa virus budding. J Virol 80:4191–4195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Pinschewer DD, Perez M, Sanchez AB, de la Torre JC (2003) Recombinant lymphocytic choriomeningitis virus expressing vesicular stomatitis virus glycoprotein. Proc Natl Acad Sci U S A 100:7895–7900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Beyer WR, Popplau D, Garten W, von Laer D, Lenz O (2003) Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P. J Virol 77:2866–2872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rojek JM, Sanchez AB, Nguyen NT, de la Torre JC, Kunz S (2008) Different mechanisms of cell entry by human-pathogenic Old World and New World arenaviruses. J Virol 82:7677–7687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Lee KJ, Perez M, Pinschewer DD, de la Torre JC (2002) Identification of the lymphocytic choriomeningitis virus (LCMV) proteins required to rescue LCMV RNA analogs into LCMV-like particles. J Virol 76:6393–6397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Ortiz-Riano E, Cheng BY, de la Torre JC, Martinez-Sobrido L (2012) Self-association of lymphocytic choriomeningitis virus nucleoprotein is mediated by its N-terminal region and is not required for its anti-interferon function. J Virol 86:3307–3317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ortiz-Riano E, Cheng BY, de la Torre JC, Martinez-Sobrido L (2011) The C-terminal region of lymphocytic choriomeningitis virus nucleoprotein contains distinct and segregable functional domains involved in NP-Z interaction and counteraction of the type I interferon response. J Virol 85:13038–13048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Pythoud C, Rodrigo WW, Pasqual G, Rothenberger S, Martinez-Sobrido L et al (2012) Arenavirus nucleoprotein targets interferon regulatory factor-activating kinase IKKepsilon. J Virol 86:7728–7738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Martinez-Sobrido L, Emonet S, Giannakas P, Cubitt B, Garcia-Sastre A et al (2009) Identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 83:11330–11340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Martinez-Sobrido L, Giannakas P, Cubitt B, Garcia-Sastre A, de la Torre JC (2007) Differential inhibition of type I interferon induction by arenavirus nucleoproteins. J Virol 81:12696–12703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Martinez-Sobrido L, Zuniga EI, Rosario D, Garcia-Sastre A, de la Torre JC (2006) Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 80:9192–9199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Borrow P, Martinez-Sobrido L, de la Torre JC (2010) Inhibition of the type I interferon antiviral response during arenavirus infection. Viruses 2:2443–2480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pythoud C, Rothenberger S, Martinez-Sobrido L, de la Torre JC, Kunz S (2015) Lymphocytic choriomeningitis virus differentially affects the virus-induced type I interferon response and mitochondrial apoptosis mediated by RIG-I/MAVS. J Virol 89:6240–6250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rodrigo WW, Ortiz-Riano E, Pythoud C, Kunz S, de la Torre JC et al (2012) Arenavirus nucleoproteins prevent activation of nuclear factor kappa B. J Virol 86:8185–8197

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Igonet S, Vaney MC, Vonrhein C, Bricogne G, Stura EA et al (2011) X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation. Proc Natl Acad Sci U S A 108:19967–19972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Burri DJ, da Palma JR, Kunz S, Pasquato A (2012) Envelope glycoprotein of arenaviruses. Viruses 4:2162–2181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cao W, Henry MD, Borrow P, Yamada H, Elder JH et al (1998) Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Science 282:2079–2081

    Article  CAS  PubMed  Google Scholar 

  81. Kunz S, Borrow P, Oldstone MB (2002) Receptor structure, binding, and cell entry of arenaviruses. Curr Top Microbiol Immunol 262:111–137

    CAS  PubMed  Google Scholar 

  82. Kunz S, Sevilla N, McGavern DB, Campbell KP, Oldstone MB (2001) Molecular analysis of the interaction of LCMV with its cellular receptor [alpha]-dystroglycan. J Cell Biol 155:301–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D et al (2007) Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446:92–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pasqual G, Rojek JM, Masin M, Chatton JY, Kunz S (2011) Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport. PLoS Pathog 7:e1002232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Capul AA, Perez M, Burke E, Kunz S, Buchmeier MJ et al (2007) Arenavirus Z-glycoprotein association requires Z myristoylation but not functional RING or late domains. J Virol 81:9451–9460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Perez M, Greenwald DL, de la Torre JC (2004) Myristoylation of the RING finger Z protein is essential for arenavirus budding. J Virol 78:11443–11448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Strecker T, Maisa A, Daffis S, Eichler R, Lenz O et al (2006) The role of myristoylation in the membrane association of the Lassa virus matrix protein Z. Virol J 3:93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Loureiro ME, D’Antuono A, Levingston Macleod JM, Lopez N (2012) Uncovering viral protein-protein interactions and their role in arenavirus life cycle. Viruses 4:1651–1667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. de la Torre JC (2008) Reverse genetics approaches to combat pathogenic arenaviruses. Antiviral Res 80:239–250

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Emonet SE, Urata S, de la Torre JC (2011) Arenavirus reverse genetics: new approaches for the investigation of arenavirus biology and development of antiviral strategies. Virology 411:416–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cheng, B. Y., Ortiz-Riano, E., de la Torre, J. C. & Martinez-Sobrido, L. Arenavirus Genome Rearrangement for the Development of Live Attenuated Vaccines. Journal of virology 89, 7373–7384, doi:10.1128/JVI.00307-15 (2015).

    Google Scholar 

  92. Ortiz-Riano E, Cheng BY, de la Torre JC, Martinez-Sobrido L (2012) D471G mutation in LCMV-NP affects its ability to self-associate and results in a dominant negative effect in viral RNA synthesis. Viruses 4:2137–2161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Russier M, Reynard S, Carnec X, Baize S (2014) The exonuclease domain of Lassa virus nucleoprotein is involved in antigen-presenting-cell-mediated NK cell responses. J Virol 88:13811–13820

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Reynard S, Russier M, Fizet A, Carnec X, Baize S (2014) Exonuclease domain of the Lassa virus nucleoprotein is critical to avoid RIG-I signaling and to inhibit the innate immune response. J Virol 88:13923–13927

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Seregin AV, Yun NE, Miller M, Aronson J, Smith JK et al (2015) The glycoprotein precursor gene of Junin virus determines the virulence of Romero strain and attenuation of Candid #1 strain in a representative animal model of Argentine Hemorrhagic Fever. J Virol 89:5949–5956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ortiz-Riano E, Cheng BY, Carlos de la Torre J, Martinez-Sobrido L (2013) Arenavirus reverse genetics for vaccine development. J Gen Virol 94:1175–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Cheng BY, Ortiz-Riano E, de la Torre JC, Martinez-Sobrido L (2013) Generation of recombinant arenavirus for vaccine development in FDA-approved Vero cells. J Vis Exp 78:e50662

    Google Scholar 

  98. Cheng, B. Y., Ortiz-Riano, E., Nogales, A., de la Torre, J. C. & Martinez-Sobrido, L. Development of liveattenuated arenavirus vaccines based on codon deoptimization. Journal of virology, doi:10.1128/JVI.03401-14 (2015).

    Google Scholar 

  99. Rodrigo WW, de la Torre JC, Martinez-Sobrido L (2011) Use of single-cycle infectious lymphocytic choriomeningitis virus to study hemorrhagic fever arenaviruses. J Virol 85:1684–1695

    Article  CAS  PubMed  Google Scholar 

  100. Emonet SF, Garidou L, McGavern DB, de la Torre JC (2009) Generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interest. Proc Natl Acad Sci U S A 106:3473–3478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Popkin DL, Teijaro JR, Lee AM, Lewicki H, Emonet S et al (2011) Expanded potential for recombinant trisegmented lymphocytic choriomeningitis viruses: protein production, antibody production, and in vivo assessment of biological function of genes of interest. J Virol 85:7928–7932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Flatz L, Hegazy AN, Bergthaler A, Verschoor A, Claus C et al (2010) Development of replication-defective lymphocytic choriomeningitis virus vectors for the induction of potent CD8+ T cell immunity. Nat Med 16:339–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Salvato M, Borrow P, Shimomaye E, Oldstone MB (1991) Molecular basis of viral persistence: a single amino acid change in the glycoprotein of lymphocytic choriomeningitis virus is associated with suppression of the antiviral cytotoxic T-lymphocyte response and establishment of persistence. J Virol 65:1863–1869

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Nisii C, Castilletti C, Raoul H, Hewson R, Brown D et al (2013) Biosafety Level-4 laboratories in Europe: opportunities for public health, diagnostics, and research. PLoS Pathog 9:e1003105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–199

    Article  CAS  PubMed  Google Scholar 

  106. Flatz L, Bergthaler A, de la Torre JC, Pinschewer DD (2006) Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA. Proc Natl Acad Sci U S A 103:4663–4668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Heix J, Grummt I (1995) Species specificity of transcription by RNA polymerase I. Curr Opin Genet Dev 5:652–656

    Article  CAS  PubMed  Google Scholar 

  108. Hess RD, Weber F, Watson K, Schmitt S (2012) Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines. Vaccine 30:2715–2727

    Article  CAS  PubMed  Google Scholar 

  109. Martinez-Sobrido L, Cadagan R, Steel J, Basler CF, Palese P et al (2010) Hemagglutinin-pseudotyped green fluorescent protein-expressing influenza viruses for the detection of influenza virus neutralizing antibodies. J Virol 84:2157–2163

    Article  CAS  PubMed  Google Scholar 

  110. Baker SF, Guo H, Albrecht RA, Garcia-Sastre A, Topham DJ et al (2013) Protection against lethal influenza with a viral mimic. J Virol 87:8591–8605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Perez M, de la Torre JC (2003) Characterization of the genomic promoter of the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 77:1184–1194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Pinschewer DD, Perez M, de la Torre JC (2005) Dual role of the lymphocytic choriomeningitis virus intergenic region in transcription termination and virus propagation. J Virol 79:4519–4526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Kranzusch PJ, Whelan SP (2011) Arenavirus Z protein controls viral RNA synthesis by locking a polymerase-promoter complex. Proc Natl Acad Sci U S A 108:19743–19748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sanchez AB, Perez M, Cornu T, de la Torre JC (2005) RNA interference-mediated virus clearance from cells both acutely and chronically infected with the prototypic arenavirus lymphocytic choriomeningitis virus. J Virol 79:11071–11081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bergeron E, Chakrabarti AK, Bird BH, Dodd KA, McMullan LK et al (2012) Reverse genetics recovery of Lujo virus and role of virus RNA secondary structures in efficient virus growth. J Virol 86:10759–10765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lopez N, Jacamo R, Franze-Fernandez MT (2001) Transcription and RNA replication of tacaribe virus genome and antigenome analogs require N and L proteins: Z protein is an inhibitor of these processes. J Virol 75:12241–12251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lan S, McLay Schelde L, Wang J, Kumar N, Ly H et al (2009) Development of infectious clones for virulent and avirulent pichinde viruses: a model virus to study arenavirus-induced hemorrhagic fevers. J Virol 83:6357–6362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Patterson M, Seregin A, Huang C, Kolokoltsova O, Smith J et al (2014) Rescue of a recombinant Machupo virus from cloned cDNAs and in vivo characterization in interferon (alphabeta/gamma) receptor double knockout mice. J Virol 88:1914–1923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Neumann G, Watanabe T, Ito H, Watanabe S, Goto H et al (1999) Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 96:9345–9350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Fodor E, Devenish L, Engelhardt OG, Palese P, Brownlee GG et al (1999) Rescue of influenza A virus from recombinant DNA. J Virol 73:9679–9682

    CAS  PubMed  PubMed Central  Google Scholar 

  121. McLay L, Ansari A, Liang Y, Ly H (2013) Targeting virulence mechanisms for the prevention and therapy of arenaviral hemorrhagic fever. Antiviral Res 97:81–92

    Article  CAS  PubMed  Google Scholar 

  122. Sanchez AB, de la Torre JC (2006) Rescue of the prototypic Arenavirus LCMV entirely from plasmid. Virology 350:370–380

    Article  CAS  PubMed  Google Scholar 

  123. Nogales A, Baker SF, Martinez-Sobrido L (2015) Replication-competent influenza A viruses expressing a red fluorescent protein. Virology 476:206–216

    Article  CAS  PubMed  Google Scholar 

  124. Flick R, Hobom G (1999) Transient bicistronic vRNA segments for indirect selection of recombinant influenza viruses. Virology 262:93–103

    Article  CAS  PubMed  Google Scholar 

  125. Vieira Machado A, Naffakh N, Gerbaud S, van der Werf S, Escriou N (2006) Recombinant influenza A viruses harboring optimized dicistronic NA segment with an extended native 5′ terminal sequence: induction of heterospecific B and T cell responses in mice. Virology 345:73–87

    Article  CAS  PubMed  Google Scholar 

  126. Marschalek A, Finke S, Schwemmle M, Mayer D, Heimrich B et al (2009) Attenuation of rabies virus replication and virulence by picornavirus internal ribosome entry site elements. J Virol 83:1911–1919

    Article  CAS  PubMed  Google Scholar 

  127. Garcia-Sastre A, Muster T, Barclay WS, Percy N, Palese P (1994) Use of a mammalian internal ribosomal entry site element for expression of a foreign protein by a transfectant influenza virus. J Virol 68:6254–6261

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Goto H, Muramoto Y, Noda T, Kawaoka Y (2013) The genome-packaging signal of the influenza A virus genome comprises a genome incorporation signal and a genome-bundling signal. J Virol 87:11316–11322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Liang Y, Hong Y, Parslow TG (2005) cis-Acting packaging signals in the influenza virus PB1, PB2, and PA genomic RNA segments. J Virol 79:10348–10355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Meyer BJ, de la Torre JC, Southern PJ (2002) Arenaviruses: genomic RNAs, transcription, and replication. Curr Top Microbiol Immunol 262:139–157

    CAS  PubMed  Google Scholar 

  131. Buchmeier MJ (2002) Arenaviruses: protein structure and function. Curr Top Microbiol Immunol 262:159–173

    CAS  PubMed  Google Scholar 

  132. Young PR, Howard CR (1983) Fine structure analysis of Pichinde virus nucleocapsids. J Gen Virol 64(Pt 4):833–842

    Article  PubMed  Google Scholar 

  133. Marsh GA, Rabadan R, Levine AJ, Palese P (2008) Highly conserved regions of influenza a virus polymerase gene segments are critical for efficient viral RNA packaging. J Virol 82:2295–2304

    Article  CAS  PubMed  Google Scholar 

  134. Kohl A, Lowen AC, Leonard VH, Elliott RM (2006) Genetic elements regulating packaging of the Bunyamwera orthobunyavirus genome. J Gen Virol 87:177–187

    Article  CAS  PubMed  Google Scholar 

  135. Lavanya M, Cuevas CD, Thomas M, Cherry S, Ross SR (2013) siRNA screen for genes that affect Junin virus entry uncovers voltage-gated calcium channels as a therapeutic target. Sci Transl Med 5:204ra131

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Beyer WR, Westphal M, Ostertag W, von Laer D (2002) Oncoretrovirus and lentivirus vectors pseudotyped with lymphocytic choriomeningitis virus glycoprotein: generation, concentration, and broad host range. J Virol 76:1488–1495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Miletic H, Fischer YH, Neumann H, Hans V, Stenzel W et al (2004) Selective transduction of malignant glioma by lentiviral vectors pseudotyped with lymphocytic choriomeningitis virus glycoproteins. Hum Gene Ther 15:1091–1100

    Article  CAS  PubMed  Google Scholar 

  138. Gomme EA, Faul EJ, Flomenberg P, McGettigan JP, Schnell MJ (2010) Characterization of a single-cycle rabies virus-based vaccine vector. J Virol 84:2820–2831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Bozac A, Berto E, Vasquez F, Grandi P, Caputo A et al (2006) Expression of human immunodeficiency virus type 1 tat from a replication-deficient herpes simplex type 1 vector induces antigen-specific T cell responses. Vaccine 24:7148–7158

    Article  CAS  PubMed  Google Scholar 

  140. Tang Y, Swanstrom R (2008) Development and characterization of a new single cycle vaccine vector in the simian immunodeficiency virus model system. Virology 372:72–84

    Article  CAS  PubMed  Google Scholar 

  141. Mason PW, Shustov AV, Frolov I (2006) Production and characterization of vaccines based on flaviviruses defective in replication. Virology 351:432–443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Chang DC, Liu WJ, Anraku I, Clark DC, Pollitt CC et al (2008) Single-round infectious particles enhance immunogenicity of a DNA vaccine against West Nile virus. Nat Biotechnol 26:571–577

    Article  CAS  PubMed  Google Scholar 

  143. Halfmann P, Ebihara H, Marzi A, Hatta Y, Watanabe S et al (2009) Replication-deficient ebolavirus as a vaccine candidate. J Virol 83:3810–3815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Wainwright S, Mims CA (1967) Plaque assay for lymphocytic choriomeningitis virus based on hemadsorption interference. J Virol 1:1091–1092

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Nakajima Y, Kobayashi K, Yamagishi K, Enomoto T, Ohmiya Y (2004) cDNA cloning and characterization of a secreted luciferase from the luminous Japanese ostracod, Cypridina noctiluca. Biosci Biotechnol Biochem 68:565–570

    Article  PubMed  Google Scholar 

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Acknowledgements

Arenavirus research in LM-S laboratory was partially funded by the NIH grants RO1 AI077719 and RO3AI099681-01A1, and by the University of Rochester Drug Discovery Pilot Award Program. Research in J.C.T. laboratory is supported by grants RO1 AI047140, RO1 AI077719, and RO1 AI079665.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY, 14642, USA

    Luis Martínez-Sobrido & Benson Yee Hin Cheng

  2. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Juan Carlos de la Torre

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  1. Luis Martínez-Sobrido
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  2. Benson Yee Hin Cheng
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  3. Juan Carlos de la Torre
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Correspondence to Luis Martínez-Sobrido or Juan Carlos de la Torre .

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  1. Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, USA

    Sunil Thomas

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Martínez-Sobrido, L., Cheng, B.Y.H., de la Torre, J.C. (2016). Reverse Genetics Approaches to Control Arenavirus. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1403. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3387-7_17

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  • DOI: https://doi.org/10.1007/978-1-4939-3387-7_17

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