Lassa Fever Virus

Abstract

Lassa virus, a member of the Arenaviridae family, is an enveloped virus with a bisegmented, linear, single‐stranded ribonucleic acid genome. Infection with Lassa virus can result in a range of outcomes from a mild or asymptomatic infection to Lassa fever, a severe and often fatal viral haemorrhagic fever. Human infection with Lassa virus occurs through contact with the reservoir Mastomys natalensis or infected humans. There are an estimated 300 000–500 000 cases of Lassa fever in West Africa each year, with most recorded cases occurring in Sierra Leone and Nigeria. Presently, there is no licensed vaccine or immunotherapy available for preventing or treating this disease. Although the antiviral drug ribavirin can be beneficial, it must be administered at an early stage of infection to successfully alter the disease outcome, thereby limiting its utility.

Key Concepts:

  • Lassa virus, a member of the Arenaviridae family, is the aetiologic agent of Lassa fever.

  • Infection with Lassa virus can result in a range of outcomes from a mild or asymptomatic infection to severe and often fatal viral haemorrhagic fever.

  • Signs and symptoms of Lassa fever are highly variable, which challenges early diagnosis.

  • Lassa virus has an enveloped virion with a bisegmented, linear, single‐stranded ribonucleic acid genome.

  • The Lassa virus virion contains nucleoprotein NP, zinc protein Z, glycoproteins GP1 and GP2 and an unusually long and stable signal peptide SSP.

  • Human infection with Lassa virus occurs through contact with its reservoir Mastomys natalensis or infected humans.

  • An estimated 300 000–500 000 cases of Lassa fever occur in West Africa each year, with most recorded cases occurring in Sierra Leone and Nigeria.

  • No licensed vaccine or immunotherapy is presently available for preventing or treating Lassa fever.

  • The antiviral drug ribavirin can be beneficial, but must be administered early, limiting its utility.

Keywords: Lassa fever; Lassa virus; arenavirus; arenaviridae; viral haemorrhagic fever; Mastomys natalensis; Sierra leone; Nigeria; ribavirin

Figure 1.

Lassa virus structure showing the organisation of the surface glycoproteins GP1 and GP2, the nucleoprotein NP, the L and Z proteins. The L and S RNA segments, which actually exist in circular complexes with large amounts of NP and small numbers of molecules of L protein are also shown.

Figure 2.

The ambisense genome organisation, replication strategy and mechanism of protein synthesis are illustrated for the S RNA of LASVs. The nucleoprotein (NP) gene is encoded in the viral complementary sense at the 3′‐end of the viral genome. The glycoprotein precursor (GPC) gene is encoded at the 5′‐end of the genome in the viral sense. Synthesis of NPmRNA occurs directly from the genome template, whereas synthesis of GPCmRNA requires viral replication to produce an intermediary viral complementary antigenome RNA. The GPC is subsequently cleaved to produce GP1 and GP2 proteins. A similar RNA synthesis phenomenon occurs with the L RNA to produce both L mRNA and Z mRNA.

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References

Albarino CG, Bird BH, Chakrabarti AK et al. (2011) The major determinant of attenuation in mice of the Candid1 vaccine for Argentine hemorrhagic fever is located in the G2 glycoprotein transmembrane domain. Journal of Virology 85: 10404–10408.

Bausch DG, Demby AH, Coulibaly M et al. (2001) Lassa fever in Guinea: I. Epidemiology of human disease and clinical observations. Vector Borne and Zoonotic Diseases 1: 269–281.

Bloch A (1978) A serological survey of Lassa fever in Liberia. Bulletin of the World Health Organization 56: 811–813.

Borio CS, Bilen MF, Arguelles MH et al. (2012) Antigen vehiculization particles based on the Z protein of Junin virus. BMC Biotechnology 12: 80.

Bowen MD, Peters CJ and Nichol ST (1997) Phylogenetic analysis of the Arenaviridae: patterns of virus evolution and evidence for cospeciation between arenaviruses and their rodent hosts. Molecular Phylogenetics and Evolution 8: 301–316.

Branco LM, Boisen ML, Andersen KG et al. (2011a) Lassa hemorrhagic fever in a late term pregnancy from northern Sierra Leone with a positive maternal outcome: case report. Virology Journal 8: 404.

Branco LM, Grove JN, Boisen ML et al. (2011b) Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection. Virology Journal 8: 478.

Branco LM, Grove JN, Geske FJ et al. (2010) Lassa virus‐like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever. Virology Journal 7: 279.

Briknarova K, Thomas CJ, York J and Nunberg JH (2011) Structure of a zinc‐binding domain in the Junin virus envelope glycoprotein. Journal of Biological Chemistry 286: 1528–1536.

Cajimat MN, Milazzo ML, Haynie ML et al. (2011) Diversity and phylogenetic relationships among the North American Tacaribe serocomplex viruses (family Arenaviridae). Virology 421: 87–95.

Cashman KA, Broderick KE, Wilkerson ER et al. (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: 262–277.

Cashman KA, Smith MA, Twenhafel NA et al. (2011) Evaluation of Lassa antiviral compound ST‐193 in a guinea pig model. Antiviral Research 90: 70–79.

Coetzee CG (1975) The biology, behaviour, and ecology of Mastomys natalensis in southern Africa. Bulletin of the World Health Organization 52: 637–644.

Cummins D, McCormick JB, Bennett D et al. (1990) Acute sensorineural deafness in Lassa fever. Journal of the American Medical Association 264: 2093–2096.

Demby AH, Inapogui A, Kargbo K et al. (2001) Lassa fever in Guinea: II. Distribution and prevalence of Lassa virus infection in small mammals. Vector Borne and Zoonotic Diseases 1: 283–297.

Ehichioya DU, Asogun DA, Ehimuan J et al. (2012) Hospital‐based surveillance for Lassa fever in Edo State, Nigeria, 2005–2008. Tropical Medicine and International Health 17: 1001–1004.

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

Fisher‐Hoch SP and McCormick JB (2004) Lassa fever vaccine. Expert Review of Vaccines 3: 189–197.

Fisher‐Hoch S, McCormick JB, Sasso D and Craven RB (1988) Hematologic dysfunction in Lassa fever. Journal of Medical Virology 26: 127–135.

Fraser DW, Campbell CC, Monath TP, Goff PA and Gregg MB (1974) Lassa fever in the Eastern Province of Sierra Leone, 1970–1972. I. Epidemiologic studies. American Journal of Tropical Medicine and Hygiene 23: 1131–1139.

Gallaher WR, DiSimone C and Buchmeier MJ (2001) The viral transmembrane superfamily: possible divergence of Arenavirus and Filovirus glycoproteins from a common RNA virus ancestor. BMC Microbiology 1: 1.

Geisbert TW, Jones S, Fritz EA et al. (2005) Development of a new vaccine for the prevention of Lassa fever. PLoS Medicine 2: e183.

Hastie KM, Kimberlin CR, Zandonatti MA, MacRae IJ and Saphire EO (2011) Structure of the Lassa virus nucleoprotein reveals a dsRNA‐specific 3′ to 5′ exonuclease activity essential for immune suppression. Proceedings of the National Academy of Sciences of the USA 108: 2396–2401.

Hastie KM, Liu T, Li S et al. (2011) Crystal structure of the Lassa virus nucleoprotein‐RNA complex reveals a gating mechanism for RNA binding. Proceedings of the National Academy of Sciences of the USA 108: 19365–19370.

Hensley LE, Smith MA, Geisbert JB et al. (2011) Pathogenesis of Lassa fever in cynomolgus macaques. Virology Journal 8: 205.

Johnson KM, McCormick JB, Webb PA et al. (1987) Clinical virology of Lassa fever in hospitalized patients. Journal of Infectious Diseases 155: 456–464.

Knobloch J, McCormick JB, Webb PA et al. (1980) Clinical observations in 42 patients with Lassa fever. Tropenmed Parasitol 31: 389–398.

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

Lecompte E, Fichet‐Calvet E, Daffis S et al. (2006) Mastomys natalensis and Lassa fever, West Africa. Emerging Infectious Diseases 12: 1971–1974.

Lee AM, Pasquato A and Kunz S (2011) Novel approaches in anti‐arenaviral drug development. Virology 411: 163–169.

Lukashevich IS, Carrion R Jr, Salvato MS et al. (2008) Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non‐human primates. Vaccine 26: 5246–5254.

Lukashevich LS, Clegg JC and Sidibe K (1993) Lassa virus activity in Guinea: distribution of human antiviral antibody defined using enzyme‐linked immunosorbent assay with recombinant antigen. Journal of Medical Virology 40: 210–217.

Malhotra S, Yen JY, Honko AN et al. (2013) Transcriptional profiling of the circulating immune response to lassa virus in an aerosol model of exposure. PLOS Neglected Tropical Diseases 7: e2171.

McCormick JB and Fisher‐Hoch SP (2002) Lassa fever. Current Topics in Microbiology and Immunology 262: 75–109.

McCormick JB, King IJ, Webb PA et al. (1986) Lassa fever. Effective therapy with ribavirin. New England Journal of Medicine 314: 20–26.

McCormick JB, King IJ, Webb PA et al. (1987) A case‐control study of the clinical diagnosis and course of Lassa fever. Journal of Infectious Diseases 155: 445–455.

McCormick JB, Webb PA, Krebs JW, Johnson KM and Smith ES (1987) A prospective study of the epidemiology and ecology of Lassa fever. Journal of Infectious Diseases 155: 437–444.

Milazzo ML, Campbell GL and Fulhorst CF (2011) Novel arenavirus infection in humans United States. Emerging Infectious Diseases 17: 1417–1420.

Monath TP, Maher M, Casals J, Kissling RE and Cacciapuoti A (1974) Lassa fever in the Eastern Province of Sierra Leone, 1970–1972. II. Clinical observations and virological studies on selected hospital cases. American Journal of Tropical Medicine and Hygiene 23: 1140–1149.

Monath TP, Newhouse VF, Kemp GE, Setzer HW and Cacciapuoti A (1974) Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone. Science 185: 263–265.

Pasqual G, Rojek JM, Masin M, Chatton JY and 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 Pathogens 7: e1002232.

Peters CJ, Liu CT, Anderson GW Jr, Morrill JC and Jahrling PB (1989) Pathogenesis of viral hemorrhagic fevers: Rift Valley fever and Lassa fever contrasted. Reviews of Infectious Diseases 11(Suppl. 4): S743–S749.

Pinneo L and Pinneo R (1971) Mystery virus from Lassa. American Journal of Nursing 71: 1352–1355.

Price ME, Fisher‐Hoch SP, Craven RB and McCormick JB (1988) A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy. British Medical Journal 297: 584–587.

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

Rybak LP (1990) Deafness associated with Lassa fever. Journal of the American Medical Association 264: 2119.

Sabeti PC, Varilly P, Fry B et al. (2007) Genome‐wide detection and characterization of positive selection in human populations. Nature 449: 913–918.

Shaffer JG, Grant DS, Schieffelin JS et al. (in press) Lassa fever in post‐conflict Sierra Leone. PLoS Neglected Tropical Diseases.

Tomori O, Fabiyi A, Sorungbe A, Smith A and McCormick JB (1988) Viral hemorrhagic fever antibodies in Nigerian populations. American Journal of Tropical Medicine and Hygiene 38: 407–410.

Wolff S, Ebihara H and Groseth A (2013) Arenavirus budding: a common pathway with mechanistic differences. Viruses 5: 528–549.

Further Reading

Buchmeier MJ, de la Torre J‐C and Peters CJ (2007) Arenaviruses. In: Fields BN, Knipe DM, Howley PM et al. (eds) Fields Virology, 5th edn, vol. 2, pp. 1791–1827. Philadelphia: Lippincott Williams & Wilkins.

Fuller JG (1974) Fever!: The Hunt for A New Killer Virus. Reader's Digest Press; distributed by Boston, USA: Dutton Publishers.

Howard CR (1986) Arenaviruses. In: Zuckerman AJ (ed.) Perspectives in Medical Virology, vol. 2, pp. 1–208. Amsterdam: Elsevier.

Brés P (ed.) (1975) International symposium of arenaviral infections of public health importance. Bulletin of the World Health Organization 52: 381–766.

McCormick JB and Fisher‐Hoch S (1996) Level 4: Virus Hunters of the CDC. Atlanta: Turner.

Ross Donaldson MD (2009) The Lassa Ward: One Man's Fight Against One of the World's Deadliest Diseases. New York, USA: St. Martin's Press.

Salvato MS (1993) The Arenaviridae. London: Plenum Press.

Viruses (2012) A Special Issue on Arenaviruses. Guest Editor Prof. Dr. Stefan Kunz. Various articles: http://www.mdpi.com/journal/viruses/special_issues/arenaviruses (12 Nov 2013).

Zuckerman AJ (2011) Arenaviruses. Leiden, Amsterdam: Elsevier Publisher.

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Garry, Robert F(Apr 2014) Lassa Fever Virus. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001032.pub2]