Pathogenicity and virulence mechanisms of Lassa virus and its animal modeling, diagnostic, prophylactic, and therapeutic developments

References

• Frame JD, Gocke DJ, Baldwin JM, et al. Lassa fever, a new virus disease of man from West Africa. Am J Trop Med Hyg. 1970;19(4):670–676.
   PubMed Web of Science ®Google Scholar
• Brisse M, Ly H. Comparative structure and function analysis of the RIG-I-Like receptors: RIG-I and MDA5. Front Immunol. 2019;10. DOI:10.3389/fimmu.2019.01586.
   PubMed Web of Science ®Google Scholar
• Ibekwe T, Okokhere P, Nwegbu M, et al. Early-Onset sensorineural hearing loss in Lassa fever. Otolaryngol Head Neck Surg. 2010;143(2_suppl):232.
   Google Scholar
• Gunther S, Lenz O. Lassa Virus. Crit Rev Clin Lab Sci. 2004;357. DOI:10.1080/10408360490497456.
   Google Scholar
• Lassa Fever | CDC. (2019, January 31). Retrieved 2021 Jan 27, from https://www.cdc.gov/vhf/lassa/index.html
   Google Scholar
• Bhatt S, Gething PW, Brady OJ, et al. The global distribution and burden of dengue. Nature. 2013;496 (7446):504–507.
   PubMed Web of Science ®Google Scholar
• Jing Q, Wang M. Dengue epidemiology. Global Health J. 2019;3(2):37–45.
   Google Scholar
• Lukashevich IS, Paessler S, De La Torre JC. Lassa virus diversity and feasibility for universal prophylactic vaccine. F1000Res. 2019;8:134.
   Google Scholar
• Mylne AQN, Pigott DM, Longbottom J, et al. Mapping the zoonotic niche of Lassa fever in Africa. Trans R Soc Trop Med Hyg. 2015;109(8):483–492.
   PubMed Web of Science ®Google Scholar
• Kuhn J, Zhou X, Alioto D. 2020 taxonomic update for phylum negarnaviricota (Riboviria: orthornavirae), including the large orders bunyavirales and mononegavirales. Arch Virol. 2020;165(12):3023–3072.
   PubMedGoogle Scholar
• Radoshitzky SR, Bào YĪ, Buchmeier MJ, et al. Past, present, and future of arenavirus taxonomy. Arch Virol. 2015;160(7):1851–1874.
   PubMed Web of Science ®Google Scholar
• Radoshitzky SR, Buchmeier MJ, Charrel RN, et al. ICTV virus taxonomy profile: arenaviridae. J Gen Virol. 2019;100(8):1200–1201.
   PubMed Web of Science ®Google Scholar
• Ibukun FI. Inter-Lineage variation of lassa virus glycoprotein epitopes: a challenge to Lassa virus vaccine development. Viruses. 2020;12(4):386.
   PubMed Web of Science ®Google Scholar
• Oloniniyi OK, Unigwe US, Okada S, et al. Genetic characterization of Lassa virus strains isolated from 2012 to 2016 in southeastern Nigeria. PLoS Negl Trop Dis. 2018;12(11):e0006971.
   PubMed Web of Science ®Google Scholar
• Ehichioya DU, Dellicour S, Pahlmann M, et al. Phylogeography of Lassa Virus in Nigeria. J Virol. 2019;93(21): N/A. DOI:10.1128/jvi.00929-19.
   Google Scholar
• Forni D, Sironi M. Population structure of Lassa mammarenavirus in West Africa. Viruses. 2020;12(4):437.
   PubMed Web of Science ®Google Scholar
• Bowen MD, Rollin PE, Ksiazek TG, et al. Genetic diversity among Lassa virus strains. J Virol. 2000;74 (15):6992–7004.
   PubMed Web of Science ®Google Scholar
• Huang Q, Liu X, Brisse M, et al. Effect of strain variations on Lassa virus Z protein-mediated human RIG-I inhibition. Viruses. 2020;12(9):907.
   PubMed Web of Science ®Google Scholar
• Xing J, Ly H, Liang Y. The Z proteins of pathogenic but not nonpathogenic arenaviruses Inhibit RIG-i-Like receptor-dependent interferon production. J Virol. 2014;89(5):2944–2955.
   PubMed Web of Science ®Google Scholar
• Auperin DD, Romanowski V, Galinski M, et al. Sequencing studies of pichinde arenavirus S RNA indicate a novel coding strategy, an ambisense viral S RNA. J Virol. 1984;52(3):897–904.
   PubMed Web of Science ®Google Scholar
• Campbell Dwyer EJ, Lai HK, MacDonald RC, et al. The Lymphocytic choriomeningitis virus RING protein Z associates with eukaryotic initiation factor 4E and selectively represses translation in a RING-dependent manner. J Virol. 2000;74(7):3293–3300.
   PubMed Web of Science ®Google Scholar
• Fan L, Briese T, Lipkin WI. Z proteins of new world arenaviruses bind RIG-I and interfere with type i interferon induction. J Virol. 2009;84(4):1785–1791.
   PubMed Web of Science ®Google Scholar
• Fehling S, Lennartz F, Strecker T. Multifunctional nature of the arenavirus RING finger protein Z. Viruses. 2012;4(11):2973–3011.
   PubMed Web of Science ®Google Scholar
• Volpon L, Osborne MJ, Capul AA, et al. Structural characterization of the Z RING-eIF4E complex reveals a distinct mode of control for eIF4E. Proc Nat Acad Sci. 2010;107(12):5441–5446.
   PubMed Web of Science ®Google Scholar
• Hastie KM, Kimberlin CR, Zandonatti MA, et al. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3ʹ to 5ʹ exonuclease activity essential for immune suppression. Proc Nat Acad Sci. 2011;108 (6):2396–2401.
   PubMed Web of Science ®Google Scholar
• Qi X, Lan S, Wang W, et al. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature. 2010;468(7325):779–783.
   PubMed Web of Science ®Google Scholar
• Cao W, Henry MD, Borrow P. Identification of - dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Science. 1998;282 (5396):2079–2081.
   PubMed Web of Science ®Google Scholar
• Kunz S, Campbell KP, Oldstone MBA. α-Dystroglycan can mediate arenavirus infection in the absence of β- dystroglycan. Virology. 2003;316(2):213–220.
   PubMed Web of Science ®Google Scholar
• Jae LT, Raaben M, Herbert AS, et al. Lassa virus entry requires a trigger-induced receptor switch. Science. 2014;344(6191):1506–1510.
   PubMed Web of Science ®Google Scholar
• Hulseberg CE, Fénéant L, Szymańska KM, et al. Lamp1 increases the efficiency of lassa virus infection by promoting fusion in less acidic endosomal compartments. MBio. 2018;9(1): N/A. DOI:10.1128/mbio.01818-17.
   PubMed Web of Science ®Google Scholar
• Singh MK, Fuller-Pace FV, Buchmeier MJ, et al. Analysis of the genomic l rna segment from lymphocytic choriomeningitis virus. Virology. 1987;161 (2):448–456.
   PubMed Web of Science ®Google Scholar
• Wallat GD, Huang Q, Wang W, et al. High-Resolution structure of the N-terminal endonuclease domain of the Lassa virus L polymerase in complex with magnesium ions. PLoS ONE. 2014;9(2):e87577.
   PubMed Web of Science ®Google Scholar
• Leung WC, Ghosh HP, Rawls WE. Journal of virology. Strandedness Pichinde Virus RNA. 1977;22 (1):235–237.
   Google Scholar
• Pinschewer DD, Perez M, De La Torre JC. Role of the virus nucleoprotein in the regulation of lymphocytic choriomeningitis virus transcription and RNA replication. J Virol. 2003;77(6):3882–3887.
   PubMed Web of Science ®Google Scholar
• King BR, Samacoits A, Eisenhauer PL, et al. Visualization of arenavirus RNA species in individual cells by single-molecule fluorescencein situhybridization suggests a model of cyclical infection and clearance during persistence. J Virol. 2018;92(12): N/A. DOI:10.1128/jvi.02241-17.
   Web of Science ®Google Scholar
• Beyer WR, Pöpplau D, Garten W, et al. Endoproteolytic Process Lymphocytic Choriomeningitis Virus Glycoprotein Subtilase SKI-1/S1P. Journal of virology. 2003;77(5):2866–2872.
   PubMed Web of Science ®Google Scholar
• Eichler R, Lenz O, Strecker T, et al. Identification of Lassa virus glycoprotein signal peptide as a trans -acting maturation factor. EMBO Rep. 2003;4(11):1084–1088.
   PubMed Web of Science ®Google Scholar
• Eichler R, Lenz O, Strecker T, et al. Signal peptide of Lassa virus glycoprotein GP-C exhibits an unusual length. FEBS Lett. 2003;538(1–3):203–206.
   PubMed Web of Science ®Google Scholar
• Kunz S, Edelmann KH, De La Torre J-C, et al. Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions. Virology. 2003;314(1):168–178.
   PubMed Web of Science ®Google Scholar
• York J, Romanowski V, Lu M, et al. The signal peptide of the junín arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex. J Virol. 2004;78 (19):10783–10792.
   PubMed Web of Science ®Google Scholar
• Lenz O, Ter Meulen J, Klenk H-D, et al. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Nat Acad Sci. 2001;98(22):12701–12705.
   PubMed Web of Science ®Google Scholar
• Torriani G, Galan-Navarro C, Kunz S. Lassa virus cell entry reveals new aspects of virus-host cell interaction. J Virol. 2017;91(4). DOI:10.1128/jvi.01902-16
   Web of Science ®Google Scholar
• A Trial to Evaluate the Optimal Dose of MV-LASV - No Study Results Posted - ClinicalTrials.gov. (2021, January 27). Retrieved 2021 Feb 18, from https://clinicaltrials.gov/ct2/show/results/NCT04055454
   Google Scholar
• Messina EL, York J, Nunberg JH. Dissection of the role of the stable signal peptide of the arenavirus envelope glycoprotein in membrane fusion. J Virol. 2012;86 (11):6138–6145.
   PubMed Web of Science ®Google Scholar
• Rojek JM, Kunz S. Cell entry by human pathogenic arenaviruses. Cell Microbiol. 2008;10(4):828–835.
   PubMed Web of Science ®Google Scholar
• Von Heijne G. Signal sequences. J Mol Biol. 1985;184 (1):99–105.
   PubMed Web of Science ®Google Scholar
• Lyko F, Martoglio B, Jungnickel B, et al. Signal Sequence processing in rough microsomes. J Biol Chem. 1995;270(34):19873–19878.
   PubMed Web of Science ®Google Scholar
• Froeschke M, Basler M, Groettrup M, et al. Long-lived signal peptide of lymphocytic choriomeningitis virus glycoprotein pGP-C. J Biol Chem. 2003;278 (43):41914–41920.
   PubMed Web of Science ®Google Scholar
• Urata S, Yasuda J. Molecular mechanism of arenavirus assembly and budding. Viruses. 2012;4(10):2049–2079.
   PubMed Web of Science ®Google Scholar
• Perez M, Craven RC, De La Torre JC. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Nat Acad Sci. 2003;100(22):12978–12983.
   PubMed Web of Science ®Google Scholar
• Lassa fever. (2017, July 31). Retrieved 2021 Jun 28, from https://www.who.int/news-room/fact-sheets/detail/lassa-fever
   Google Scholar
• loIacono G, Cunningham AA, Fichet-Calvet E, et al. Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of Lassa fever. PLoS Negl Trop Dis. 2015;9(1):e3398.
   PubMed Web of Science ®Google Scholar
• Forni D, Pontremoli C, Pozzoli U, et al. Ancient evolution of mammarenaviruses: adaptation via changes in the L protein and no evidence for host–virus codivergence. Genome Biol Evol. 2018;10(3):863–874.
   PubMed Web of Science ®Google Scholar
• Agbonlahor DE, Erah A, Uhunmwangho J. Prevalence of Lassa virus among rodents trapped in three South-South States of Nigeria. J Vector Borne Dis. 2017;54(2):146–150. Retrievedfromhttps://www.jvbd.org/temp/JVectorBorneDis542146-5766983_160109.pdf
   PubMed Web of Science ®Google Scholar
• Olayemi A, Cadar D, Magassouba NF, et al. New Hosts of The Lassa Virus. Sci Rep. 2016;6(1): N/A. DOI:10.1038/srep25280.
   PubMedGoogle Scholar
• Leirs H, Verhagen R, Verheyen W. The basis of reproductive seasonally in mastomys rats (Rodentia: muridae) in Tanzania. J Trop Ecol. 1994;10(1):55–66.
   Google Scholar
• Richmond JK. Lassa fever: epidemiology, clinical features, and social consequences. BMJ. 2003;327 (7426):1271–1275.
   PubMed Web of Science ®Google Scholar
• Largest-ever Lassa fever research programme launches in West Africa –. (2020, December 18). Retrieved 2021 Jun 27, from https://cepi.net/news_cepi/largest-ever-lassa-fever-research-programme-launches-in-west-africa/
   Google Scholar
• Mateer EJ, Huang C, Shehu NY, et al. Lassa fever– induced sensorineural hearing loss: a neglected public health and social burden. PLoS Negl Trop Dis. 2018;12 (2):e0006187.
   PubMed Web of Science ®Google Scholar
• Yaro CA, Kogi E, Opara KN, et al. Infection pattern, case fatality rate and spread of Lassa virus in Nigeria. BMC Infect Dis. 2021;21(1): N/A. 10.1186/s12879-021-05837-x.
   PubMed Web of Science ®Google Scholar
• Greenky D, Knust B, Dziuban EJ. What pediatricians should know about lassa virus. J AMA Pediatr. 2018;172(5):407.
   PubMed Web of Science ®Google Scholar
• McCormick JB (2008). Encyclopedia of virology [EPub] ( Third ed., Vol. 2. 10.1016/B978-012374410-4.00436-2.
   Google Scholar
• Webb PA, McCormick JB, King IJ, et al. Lassa fever in children in Sierra Leone, West Africa. Trans R Soc Trop Med Hyg. 1986;80(4):577–582.
   PubMed Web of Science ®Google Scholar
• Workshop WHO. (2018 Accessed 23 November 2021, April). “Efficacy trials of Lassa Therapeutics: endpoints, trial design, site selection. Retrieved from https://www.who.int/docs/default-source/blue-print/lassa-therapeutics-workshop-april-25-2018.pdf?sfvrsn=fb777089_2
   Google Scholar
• Yuill TM & University of Wisconsin-Madison. (2020, March). Lassa Fever. Retrieved 2020 Dec 10, from https://www.merckmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/lassa-fever
   Google Scholar
• Johnson KM, McCormick JB, Webb PA, et al. Clinical virology of Lassa fever in hospitalized patients. J Infect Dis. 1987;155(3):456–464.
   PubMed Web of Science ®Google Scholar
• Kayem ND, Benson C, Aye CYL, et al. Lassa fever in pregnancy: a systematic review and meta-analysis. Trans R Soc Trop Med Hyg. 2020;114(5):385–396.
   PubMed Web of Science ®Google Scholar
• Asogun DA, Adomeh DI, Ehimuan J, et al. Molecular diagnostics for Lassa fever at irrua specialist teaching hospital, Nigeria: lessons learnt from two years of laboratory operation. PLoS Negl Trop Dis. 2012;6(9):e1839.
   PubMed Web of Science ®Google Scholar
• Branco LM, Grove JN, Geske FJ, et al. Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever. Virol J. 2010;7(1):279.
   PubMedGoogle Scholar
• Bello OO, Akinajo OR, Odubamowo KH, et al. (2016). Lassa fever in pregnancy: report of 2 cases seen at the university college hospital, Ibadan. Case Reports in Obstetrics and Gynecology, 2016, 1–3.
   Google Scholar
• Khan SH, Goba A, Chu M, et al. New opportunities for field research on the pathogenesis and treatment of Lassa fever. Antiviral Res. 2008;78(1):103–115.
   PubMed Web of Science ®Google Scholar
• Agboeze J, Nwali MI, Nwakpakpa E, et al. Lassa fever in pregnancy with a positive maternal and fetal outcome: a case report. Inter J Infect Dis. 2019;89:84–86.
   PubMed Web of Science ®Google Scholar
• Branco LM, Boisen ML, Andersen KG, et al. Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report. Virol J. 2011;8(1):404.
   PubMedGoogle Scholar
• Okogbenin S, Okoeguale J, Akpede G, et al. Retrospective cohort study of lassa fever in pregnancy, Southern Nigeria. Emerg Infect Dis. 2019;25 (8):1494–1500.
   PubMed Web of Science ®Google Scholar
• Akhuemokhan OC, Ewah-Odiase RO, Akpede N, et al. Prevalence of Lassa Virus Disease (LVD) in Nigerian children with fever or fever and convulsions in an endemic area. PLoS Negl Trop Dis. 2017;11(7): e0005711.
   PubMed Web of Science ®Google Scholar
• Ogunkunle TO, Bello SO, Anderson CI, et al. Fatal case of newborn Lassa fever virus infection mimicking late onset neonatal sepsis: a case report from northern Nigeria. Infect Dis Poverty. 2020;9(1): N/A. DOI:10.1186/s40249-020-00731-1.
   PubMed Web of Science ®Google Scholar
• Monson MH, Frame JD, Cole AK, et al. Pediatric Lassa fever: a review of 33 Liberian cases. Am J Trop Med Hyg. 1987;36(2):408–415.
   PubMed Web of Science ®Google Scholar
• Akpede GO, Kayode-Adedeji BO, Dawodu SO. Manifestations and outcomes of lassa fever in Nigerian children: a case series. Arch Dis Child. 2012;97(Suppl1):A38.3–A39.
   Google Scholar
• Sattler RA, Paessler S, Ly H, et al. Animal Models of Lassa Fever. Pathogens. 2020;9(3):197.
   PubMed Web of Science ®Google Scholar
• Walker DH, McCormick JB. Pathologic and virologic study of fatal Lassa fever in man. Am J Pathol: Cell Mol Biol Dis, 1982;107(3):349–356. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1916239/
   Google Scholar
• McCormick JB, King IJ, Webb PA, et al. Lassa Fever. N Engl J Med. 1986; 314(1):20–26.[82]Cummins D. Acute sensorineural deafness in Lassa fever. J AMA. 1990;264(16):2093–2096.
   Google Scholar
• Cummins D. Acute sensorineural deafness in Lassa fever. J AMA. 1990;264(16):2093–2096.
   PubMed Web of Science ®Google Scholar
• Härkönen K, Kivekäs I, Rautiainen M, et al. Quality of life and hearing eight years after sudden sensorineural hearing loss. Laryngoscope. 2016;127(4):927–931.
   PubMed Web of Science ®Google Scholar
• Wilson WR, Veltri RW, Laird N, et al. Viral and epidemiologic studies of idiopathic sudden hearing loss. Otolaryngol Head Neck Surg. 1983;91(6):653–658.
   PubMed Web of Science ®Google Scholar
• Okokhere PO, Ibekwe TS, Akpede GO. Sensorineural hearing loss in Lassa fever: two case reports. J Med Case Rep. 2009;3(1):N/A. 10.1186/1752-1947-3-36.
   PubMedGoogle Scholar
• Ficenec SC, Percak J, Arguello S, et al. Lassa fever induced hearing loss: the neglected disability of hemorrhagic fever. Inter J Infect Dis. 2020;100:82–87.
   PubMed Web of Science ®Google Scholar
• Mertens PE, Patton R, Baum JJ, et al. Clinical presentation of lassa fever cases during the hospital epidemic at Zorzor, Liberia, March-April 1972 *. Am J Trop Med Hyg. 1973;22(6):780–784.
   PubMed Web of Science ®Google Scholar
• White HA. Lassa fever A study of 23 hospital cases. Trans R Soc Trop Med Hyg. 1972;66(3):390–398.
   PubMed Web of Science ®Google Scholar
• Yun NE, Ronca S, Tamura A, et al. Animal model of sensorineural hearing loss associated with Lassa virus infection. J Virol. 2015;90(6):2920–2927.
   PubMed Web of Science ®Google Scholar
• Cashman KA, Wilkinson ER, Zeng X, et al. Immune- mediated systemic vasculitis as the proposed cause of sudden-onset sensorineural hearing loss following Lassa virus exposure in cynomolgus macaques. MBio. 2018;9(5): N/A.10.1128/mbio.01896-18.
   PubMed Web of Science ®Google Scholar
• Töndury G, Smith DW. Fetal rubella pathology. J Pediatr. 1966; 68(6):867–879.[92]Webster WS. Teratogen update: congenital rubella. Teratology. 1998;58(1):13–23.
   Google Scholar
• Webster WS. Teratogen update: congenital rubella. Teratology. 1998;58(1):13–23.
   PubMedGoogle Scholar
• Hensley LE, Smith MA, Geisbert JB, et al. Pathogenesis of lassa fever in cynomolgus macaques. Virol J. 2011;8 (1):205.
   PubMedGoogle Scholar
• Lukashevich IS, Maryankova R, Vladyko AS, et al. Lassa and mopeia virus replication in human monocytes/macrophages and in endothelial cells: different effects on IL-8 and TNF-? gene expression.J Med Virol. 1999;59(4):552–560.
   PubMed Web of Science ®Google Scholar
• Mahanty S, Hutchinson K, Agarwal S, et al. Cutting edge: impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. J Immunol. 2003;170(6):2797–2801.
   PubMed Web of Science ®Google Scholar
• Walker DH, Lange JV, Murphy FA. Comparative pathology of Lassa virus infection in monkeys, Guinea-pigs, and Mastomys natalensis. Bull World Health Organ. 1975;53(4–6):523–534.Retrievedfromhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2366626/
   Google Scholar
• Baize S, Kaplon J, Faure C, et al. Lassa virus infection of human dendritic cells and macrophages is productive but fails to activate cells. J Immunol. 2004;172 (5):2861–2869.
   PubMed Web of Science ®Google Scholar
• Hawiger D, Inaba K, Dorsett Y, et al. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med. 2001;194 (6):769–780.
   PubMed Web of Science ®Google Scholar
• Baize S, Marianneau P, Loth P, et al. Early and strong immune responses are associated with control of viral replication and recovery in Lassa virus-infected cynomolgus monkeys. J Virol. 2009;83(11):5890–5903.
   PubMed Web of Science ®Google Scholar
• Hallam HJ, Hallam S, Rodriguez SE, et al. Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development. Npj Vaccines. 2018;3(1): N/A. DOI:10.1038/s41541-018-0049-5.
   PubMedGoogle Scholar
• Günther S, Kühle O, Rehder D, et al. Antibodies to Lassa virus Z protein and nucleoprotein co-occur in human sera from Lassa fever endemic regions. Med Microbiol Immunol. 2001;189(4):225–229.
   PubMed Web of Science ®Google Scholar
• Meulen J, Badusche M, Kuhnt K, et al. Characterization of Human CD4+ T-Cell clones recognizing conserved and variable epitopes of the lassa virus nucleoprotein. J Virol. 2000;74(5):2186–2192.
   PubMed Web of Science ®Google Scholar
• Yun NE, Walker DH. Pathogenesis of Lassa fever. Viruses. 2012;4(10):2031–2048.
   PubMed Web of Science ®Google Scholar
• Fisher-Hoch SP, Hutwagner L, Brown B, et al. Effective vaccine for Lassa fever. J Virol. 2000;74(15):6777–6783.
   PubMed Web of Science ®Google Scholar
• Lukashevich IS, Carrion R, Salvato MS, et al. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates. Vaccine. 2008;26(41):5246–5254.
   PubMed Web of Science ®Google Scholar
• Flatz L, Rieger T, Merkler D, et al. T cell-dependence of Lassa fever pathogenesis. PLoS Pathog. 2010;6(3): e1000836.
   PubMed Web of Science ®Google Scholar
• Maurice NJ, McElrath MJ, Andersen-Nissen E, et al. CXCR3 enables recruitment and site-specific bystander activation of memory CD8+ T cells. Nat Commun. 2019;10(1): N/A. DOI:10.1038/s41467-019-12980-2.
   Google Scholar
• Port JR, Wozniak DM, Oestereich L, et al. Severe human Lassa fever is characterized by nonspecific T-cell activation and lymphocyte homing to inflamed tissues. J Virol. 2020;94(21): N/A. DOI:10.1128/jvi.01367-20.
   PubMed Web of Science ®Google Scholar
• Ostler T, Pircher H, Ehl S. Bystander” recruitment of systemic memory T cells delays the immune response to respiratory virus infection. Eur J Immunol. 2003;33 (7):1839–1848.
   PubMed Web of Science ®Google Scholar
• Oestereich L, Rieger T, Lüdtke A, et al. Efficacy of favipiravir alone and in combination with ribavirin in a lethal, immunocompetent mouse model of lassa fever. J Infect Dis. 2015;213(6):934–938.
   PubMed Web of Science ®Google Scholar
• Meyer B, Groseth A. Apoptosis during arenavirus infection: mechanisms and evasion strategies. Microbes Infect. 2018;20(2):65–80.
   PubMed Web of Science ®Google Scholar
• Huang Q, Shao J, Lan S, et al. VitroandIn VivoCharacterizations of pichinde viral nucleoprotein exoribonuclease functions. J Virol. 2015;89 (13):6595–6607.
   PubMed Web of Science ®Google Scholar
• Reynard S, Russier M, Fizet A, et al. Exonuclease domain of the Lassa virus nucleoprotein is critical to avoid RIG-I signaling and to inhibit the innate immune response. J Virol. 2014;88(23):13923–13927.
   PubMed Web of Science ®Google Scholar
• Rodrigo WWSI, Ortiz-Riano E, Pythoud C, et al. Arenavirus Nucleoproteins Prevent Activation of Nucl Factor Kappa B. Journal of Virology. 2012;86 (15):8185–8197.
   PubMed Web of Science ®Google Scholar
• Carnec X, Baize S, Reynard S, et al. Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust type I interferon response in human dendritic cells and macrophages. J Virol. 2011;85 (22):12093–12097.
   PubMed Web of Science ®Google Scholar
• Prescott JB, Marzi A, Safronetz D, et al. Immunobiology of Ebola and Lassa virus infections. Nat Rev Immunol. 2017;17(3):195–207.
   PubMed Web of Science ®Google Scholar
• Rehwinkel J, Gack MU. RIG-I-like receptors: their regulation and roles in RNA sensing. Nat Rev Immunol. 2020;20(9):537–551.
   PubMed Web of Science ®Google Scholar
• Stott RJ, Strecker T, Foster TL. Distinct molecular mechanisms of host immune response modulation by arenavirus NP and Z proteins. Viruses. 2020;12(7):784.
   PubMed Web of Science ®Google Scholar
• Bevilacqua PC, George CX, Samuel CE, et al. Binding of the protein kinase PKR to RNAs with secondary structure defects: role of the tandem A−G mismatch and noncontiguous helixes†. Biochemistry. 1998;37 (18):6303–6316.
   PubMed Web of Science ®Google Scholar
• Huang C, Kolokoltsova OA, Mateer EJ, et al. Highly pathogenic new world arenavirus infection activates the pattern recognition receptor protein Kinase R without attenuating virus replication in human cells. J Virol. 2017;91(20). DOI:10.1128/jvi.01090-17.
   Web of Science ®Google Scholar
• Mateer EJ, Maruyama J, Card GE, et al. Lassa virus, but not highly pathogenic new world arenaviruses, restricts immunostimulatory double-stranded RNA accumulation during infection. J Virol. 2020;94(9). DOI:10.1128/jvi.02006-19.
   Web of Science ®Google Scholar
• Loureiro ME, Zorzetto-Fernandes AL, Radoshitzky S, et al. DDX3 suppresses type I interferons and favors viral replication during Arenavirus infection. PLoS Pathog. 2018;14(7):e1007125.
   PubMed Web of Science ®Google Scholar
• Garcia-Sastre A, Biron CA. Type 1 interferons and the virus-host relationship: a lesson in detente. Science. 2006;312(5775):879–882.
   PubMed Web of Science ®Google Scholar
• Marie I. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 1998;17 (22):6660–6669.
   PubMed Web of Science ®Google Scholar
• Mariën J, Borremans B, Gryseels S, et al. No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions. Parasit Vectors. 2017;10(1):1.
   PubMedGoogle Scholar
• Maruyama J, Manning JT, Mateer EJ, et al. Lethal infection of Lassa virus isolated from a human clinical sample in outbred guinea pigs without adaptation. MSphere. 2019;4(5). DOI:10.1128/msphere.00428-19
   Web of Science ®Google Scholar
• Maruyama J, Mateer EJ, Manning JT, et al. Adenovirus vector-based vaccine is fully protective against lethal Lassa fever challenge in Hartley Guinea pigs. Vaccine. 2019;37(45):6824–6831.
   PubMed Web of Science ®Google Scholar
• Oestereich L, Lüdtke A, Ruibal P, et al. Chimeric mice with competent hematopoietic immunity reproduce key features of severe Lassa fever. PLoS Pathog. 2016;12(5):e1005656.
   PubMed Web of Science ®Google Scholar
• Golden JW, Hammerbeck CD, Mucker EM, et al. Animal models for the study of rodent-borne hemorrhagic fever viruses: arenaviruses and hantaviruses. Biomed Res Int. 2015;(2015:1–31.
   Web of Science ®Google Scholar
• Jahrling PB, Hesse RA, Eddy GA, et al. Lassa virus infection of rhesus monkeys: pathogenesis and treatment with Ribavirin. J Infect Dis. 1980;141(5):580–589.
   PubMed Web of Science ®Google Scholar
• Lange JV, Mitchell SW, Evatt BL, et al. Kinetic study of platelets and fibrinogen in Lassa virus-infected monkeys and early pathologic events in Mopeia virus-infected monkeys. Am J Trop Med Hyg. 1985;34(5):999–1007.
   PubMed Web of Science ®Google Scholar
• Lan S, Shieh WJ, Huang Q, et al. Virulent infection of outbred hartley guinea pigs with recombinant pichinde virus as a surrogate small animal model for human Lassa fever. Virulence. 2020;11(1):1131–1141.
   PubMed Web of Science ®Google Scholar
• Shieh WJ, Lan S, Zaki SR, et al. Pichinde virus infection of outbred Hartley Guinea pigs as a surrogate animal model for human Lassa fever: histopathological and immunohistochemical analyses. Pathogens. 2020;9 (7):579.
   PubMed Web of Science ®Google Scholar
• Lingas G, Rosenke K, Safronetz D, et al. Lassa viral dynamics in non-human primates treated with favipiravir or ribavirin. PLoS Comput Biol. 2021;17(1): e1008535.
   PubMed Web of Science ®Google Scholar
• Hoffmann C, Wurr S, Pallasch E, et al. Experimental morogoro virus infection in its natural host, mastomys natalensis. Viruses. 2021;13(5):851. doi:10.3390/v13050851
   PubMed Web of Science ®Google Scholar
• Tang-Huau, T. L., Rosenke, K., Meade-White, K., Carmody, A., Smith, B. J., Bosio, C. M., Feldmann, H. (2021). Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice. Viruses, 13(5), 729. https://doi.org/10.3390/v13050729
   PubMed Web of Science ®Google Scholar
• sNiedrig M, Schmitz H, Becker S, et al. First international quality assurance study on the rapid detection of viral agents of bioterrorism. J Clin Microbiol. 2004;42 (4):1753–1755.
   PubMed Web of Science ®Google Scholar
• Raabe V, Koehler J, Kraft CS. Laboratory diagnosis of Lassa fever. J Clin Microbiol. 2017;55(6):1629–1637.
   PubMed Web of Science ®Google Scholar
• Mazzola LT, Kelly-Cirino C. Diagnostics for Lassa fever virus: a genetically diverse pathogen found in low-resource settings. BMJ Glob Health. 2019;4 (Suppl2):e001116.
   PubMedGoogle Scholar
• Boisen ML, Hartnett JN, Shaffer JG, et al. Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever. Sci Rep. 2018;8(1): N/A. DOI:10.1038/s41598-018-24246-w.
   Google Scholar
• Ter Meulen J, Koulemou K, Wittekindt T, et al. Detection of Lassa virus antinucleoprotein Immunoglobulin G (IgG) and IgM antibodies by a simple recombinant immunoblot assay for field use. J Clin Microbiol. 1998;36(11):3143–3148.
   PubMed Web of Science ®Google Scholar
• Happi AN, Happi CT, Schoepp RJ. Lassa fever diagnostics: past, present, and future. Curr Opin Virol. 2019;37:132–138.
   PubMed Web of Science ®Google Scholar
• Satterly NG, Voorhees MA, Ames AD, et al. Comparison of MagPix assays and enzyme-linked immunosorbent assay for detection of hemorrhagic fever viruses. J Clin Microbiol. 2016;55(1):68–78.
   PubMed Web of Science ®Google Scholar
• Adams NM, Creecy AE, Majors CE, et al. Design criteria for developing low-resource magnetic bead assays using surface tension valves. Biomicrofluidics. 2013;7(1):014104.
   PubMed Web of Science ®Google Scholar
• He J, Kraft A, Fan J, et al. Simultaneous detection of CDC Category “A” DNA and RNA bioterrorism agents by use of multiplex PCR & RT-PCR enzyme hybridization assays. Viruses. 2009;1(3):441–459.
   PubMed Web of Science ®Google Scholar
• Quan P-L, Palacios G, Jabado OJ, et al. Detection of respiratory viruses and subtype identification of influenza A viruses by greenechipresp oligonucleotide microarray. J Clin Microbiol. 2007;45(8):2359–2364.
   PubMed Web of Science ®Google Scholar
• Khan JA, Rehman S, Fisher-Hoch SP, et al. Crimean Congo-Haemorrhagic fever treated with oral ribavirin. Lancet. 1995;346(8973):472–475.
   PubMed Web of Science ®Google Scholar
• Mardani M, Jahromi MK, Naieni KH, et al. The efficacy of Oral Ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran. Clinl Infect Dis. 2003;36(12):1613–1618.
   PubMed Web of Science ®Google Scholar
• Eberhardt KA, Mischlinger J, Jordan S, et al. Ribavirin for the treatment of Lassa fever: a systematic review and meta-analysis. Inter J Infect Dis. 2019;87:15–20.
   PubMed Web of Science ®Google Scholar
• Bausch D, Hadi C, Khan S, et al. Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis for Lassa fever. Clinl Infect Dis. 2010;51(12):1435–1441.
   PubMed Web of Science ®Google Scholar
• Bell TM, Shaia CI, Bearss JJ, et al. Temporal progression of lesions in guinea pigs infected with Lassa virus. Vet Pathol. 2016;54(3):549–562.
   PubMed Web of Science ®Google Scholar
• Falzaran D, Bente D. Animal models for viral haemorrhagic fever. Clin Microbiol Infect. 2019;21:e17–e27.
   Web of Science ®Google Scholar
• World Health Organization. (2016). Clinical management of patients with viral haemorrhagic fever: a pocket guide for front-line health workers. interim emergency guidance for Country adaption (2nd ed.). Geneva, Switzerland: World Health Organization.
   Google Scholar
• Ribavirin - LiverTox - NCBI Bookshelf. (2018, June 10). Retrieved 2021 Mar 30, from https://www.ncbinlm.nih.gov/books/NBK548115/
   Google Scholar
• Cashman KA, Smith MA, Twenhafel NA, et al. Evaluation of Lassa antiviral compound ST-193 in a Guinea pig model. Antiviral Res. 2011;90(1):70–79.
   PubMed Web of Science ®Google Scholar
• Gary JM, Welch SR, Ritter JM, et al. Lassa virus targeting of anterior uvea and endothelium of cornea and conjunctiva in eye of guinea pig model. Emerg Infect Dis. 2019;25(5):865–874.
   PubMed Web of Science ®Google Scholar
• Safronetz D, Rosenke K, Westover JB, et al. The broad- spectrum antiviral favipiravir protects Guinea pigs from lethal Lassa virus infection post-disease onset. Sci Rep. 2015;5(1). DOI:10.1038/srep14775.
   Web of Science ®Google Scholar
• Jahrling PB, Peters CJ. Passive antibody therapy of Lassa fever in cynomolgus monkeys: importance of neutralizing antibody and Lassa virus strain. Infect Immun. 1984;44(2):528–533.
   PubMed Web of Science ®Google Scholar
• Stephen E, Jahrling P (1979). Ribavirin treatment of Toga-, Arena- and Bunyavirus infections in subhuman primates and other laboratory animal species. U.S. Army Medical Research Institute of Infectious Disease. Published. Retrievedfromhttps://apps.dtic.mil/sti/citations/ADA083561
   Google Scholar
• Rosenke K, Feldmann H, Westover JB, et al. Use of favipiravir to treat Lassa Virus infection in macaques. Emerg Infect Dis. 2018;24(9):1696–1699.
   PubMed Web of Science ®Google Scholar
• Herring S, Oda JM, Wagoner J, et al. Inhibition of arenaviruses by combinations of orally available approved drugs. Antimicrob Agents Chemother. 2021. doi:10.1128/aac.01146-20
   Web of Science ®Google Scholar
• Hulseberg CE, Fénéant L, Szymańska-de Wijs KM, et al. Arbidol and other low-molecular-weight drugs that inhibit Lassa and Ebola viruses. J Virol. 2019;93(8). DOI: 10.1128/jvi.02185-18.
   Web of Science ®Google Scholar
• Kumar N, Sharma S, Kumar R, et al. Host-directed antiviral therapy. Clin Microbiol Rev. 2020;33(3).10.1128/cmr.00168-19.
   PubMed Web of Science ®Google Scholar
• Müller S, Günther S. Broad-Spectrum antiviral activity of small interfering RNA targeting the conserved RNA termini of Lassa virus. Antimicrob Agents Chemother. 2007;51(6):2215–2218.
   PubMed Web of Science ®Google Scholar
• Buchmeier MJ, Lewicki HA, Tomori O, et al. Monoclonal antibodies to lymphocytic choriomeningitis virus react with pathogenic arenaviruses. Nature. 1980;288(5790):486–487.
   PubMed Web of Science ®Google Scholar
• Frame JD, Verbrugge GP, Gill RG, et al. The use of Lassa fever convalescent plasma in Nigeria. Trans R Soc Trop Med Hyg. 1984;78(3):319–324.
   PubMed Web of Science ®Google Scholar
• Cross RW, Mire CE, Branco LM, et al. Treatment of Lassa virus infection in outbred Guinea pigs with first-in-class human monoclonal antibodies. Antiviral Res. 2016;133:218–222.
   PubMed Web of Science ®Google Scholar
• Mire CE, Cross RW, Geisbert JB, et al. Human- monoclonal-antibody therapy protects nonhuman primates against advanced Lassa fever. Nat Med. 2017;23 (10):1146–1149.
   PubMed Web of Science ®Google Scholar
• World Health Organization. (2017 Accessed 23 November 2021, June). WHO Target Product Profile for Lassa virus Vaccine. Retrieved from https://www.who.int/blueprint/priority-diseases/key-action/LassaVirusVaccineTPP.PDF?ua=1
   Google Scholar
• Purushotham J, Lambe T, Gilbert SC. Vaccine platforms for the prevention of Lassa fever. Immunol Lett. 2019;215:1–11.
   PubMed Web of Science ®Google Scholar
• Phase II Study to Evaluate Safety and Immunogenicity of a Chikungunya Vaccine - Full Text View - ClinicalTrials.gov. (2018, June 21). Retrieved 2021 Feb 16, from https://clinicaltrials.gov/ct2/show/NCT02861586
   Google Scholar
• Study to Evaluate the Dosage and Safety of Two Intramuscular Injections of an Investigational Clade B HIV Vaccine - Full Text View - ClinicalTrials.gov. (2012). Retrieved 2021 Mar 30, from https://clinicaltrials.gov/ct2/show/NCT01320176
   Google Scholar
• Mateo M, Reynard S, Carnec X, et al. Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot. Sci Transl Med. 2019;11(512):eaaw3163.
   PubMed Web of Science ®Google Scholar
• Mateo M, Reynard S, Journeaux A, et al. A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains. Sci Transl Med. 2021;13(597):eabf6348.
   PubMed Web of Science ®Google Scholar
• Vrba SM, Kirk NM, Brisse M, et al. Development and applications of viral vectored vaccines to combat zoonotic and emerging public health threats. Vaccines (Basel). 2020;8(4):680.
   PubMed Web of Science ®Google Scholar
• Chen J, Wang J, Zhang J, et al. Advances in development and application of influenza vaccines. Front Immunol. 2021;12:711997.
   PubMed Web of Science ®Google Scholar
• Fischer RJ, Purushotham JN, Doremalen NV, et al. ChAdOx1-vectored Lassa fever vaccine elicits a robust cellular and humoral immune response and protects Guinea pihs against lethal Lassa virus challenge. NPJ Vaccines. 2021;6(1):32.
   PubMed Web of Science ®Google Scholar
• Carrion R, Patterson JL, Johnson C, et al. A ML29 reassortant virus protects Guinea pigs against a distantly related Nigerian strain of Lassa virus and can provide sterilizing immunity. Vaccine. 2007;25 (20):4093–4102.
   PubMed Web of Science ®Google Scholar
• Carrion R, Patterson JL. An animal model that reflects human disease: the common marmoset (Callithrix jacchus). Curr Opin Virol. 2012;2(3):357–362.
   PubMed Web of Science ®Google Scholar
• Johnson DM, Cubitt B, Pfeffer TL, et al. Lassa virus vaccine candidate ML29 generates truncated viral RNAs which contribute to interfering activity and attenuation. Viruses. 2021;13(2):214.
   PubMed Web of Science ®Google Scholar
• Lukashevich I. Advanced Vaccine Candidates for Lassa Fever. Viruses. 2012;4(11):2514–2557.
   PubMed Web of Science ®Google Scholar
• Geisbert TW, Jones S, Fritz EA, et al. Development of a new vaccine for the prevention of Lassa fever. PLoS Med. 2005;2(6):e183.
   PubMed Web of Science ®Google Scholar
• Fathi A, Dahlke C, Addo MM. Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens. Hum Vaccin Immunother. 2019;15(10):2269–2285.
   PubMed Web of Science ®Google Scholar
• Cross RW, Xu R, Matassov D, et al. Quadrivalent VesiculoVax vaccine protects nonhuman primates from viral-induced hemorrhagic fever and death. J Clin Invest. 2020;130(1):539–551.
   PubMed Web of Science ®Google Scholar
• Welch SR, Scholte FEM, Albariño CG, et al. The S genome segment is sufficient to maintain pathogenicity in intra-clade Lassa virus reassortants in a guinea pig model. Front Cell Infect Microbiol. 2018;8. DOI:10.3389/fcimb.2018.00240.
   PubMed Web of Science ®Google Scholar
• Brisse ME, Ly H. Hemorrhagic fever-causing arenaviruses: lethal pathogens and potent immune suppressors. Front Immunol. 2019;10. DOI:10.3389/fimmu.2019.00372.
   Web of Science ®Google Scholar
• Jahrling PB, Smith S, Hesse RA, et al. Pathogenesis of Lassa virus infection in Guinea pigs. Infect Immun. 1982;37(2):771–778.
   PubMed Web of Science ®Google Scholar
• Yun NE, Seregin AV, Walker DH, et al. Mice lacking functional STAT1 are highly susceptible to lethal infection with Lassa virus. J Virol. 2013;87 (19):10908–10911.
   PubMed Web of Science ®Google Scholar
• Safety, Tolerability and Immunogenicity of INO-4500 in Healthy Volunteers - Full Text View - ClinicalTrials. gov. (2021). Retrieved 2021 Feb 18, from https://clinicaltrials.gov/ct2/show/NCT03805984
   Google Scholar
• Safronetz D, Mire C, Rosenke K, et al. A recombinant vesicular stomatitis virus-based lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses. PLoS Negl Trop Dis. 2015;9(4):e0003736.
   PubMed Web of Science ®Google Scholar
• Cashman, K. A., Broderick, K. E., Wilkinson, E. R., Shaia, C. I., Bell, T. M., Shurtleff, A. C., Spik, K. W., Badger, C. V., Guttieri, M. C., Sardesai, N. Y., & Schmaljohn, C. S. (2013). Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation. Vaccines, 1(3), 262–277. https://doi.org/10.3390/vaccines1030262
   Google Scholar
• Fisher-Hoch SP, McCormick JB, Auperin D, et al. Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene. Proc Nat Acad Sci. 1989;86(1):317–321.
   PubMed Web of Science ®Google Scholar
• Bredenbeek PJ, Molenkamp R, Spaan WJM, et al. A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins. Virology. 2006;345 (2):299–304.
   PubMed Web of Science ®Google Scholar
• Jiang X, Dalebout TJ, Bredenbeek PJ, et al. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in Guinea pigs. Vaccine. 2011;29(6):1248–1257.
   PubMed Web of Science ®Google Scholar
• Wang M, Jokinen J, Tretyakova I, et al. Alphavirus vector-based replicon particles expressing multivalent cross-protective Lassa virus glycoproteins. Vaccine. 2018;36(5):683–690.
   PubMed Web of Science ®Google Scholar
• McCormick JB, Mitchell SW, Kiley MP, et al. Inactivated Lassa virus elicits a non protective immune response in rhesus monkeys. J Med Virol. 1992;37(1):1–7. https://doi.org/10.1002/jmv.1890370102
   PubMed Web of Science ®Google Scholar