Sequence Variability and Geographic Distribution of Lassa Virus, Sierra Leone - Volume 21, Number 4—April 2015 - Emerging Infectious Disease journal - CDC
Volume 21, Number 4—April 2015
Sequence Variability and Geographic Distribution of Lassa Virus, Sierra Leone
Lassa fever (LF) belongs to a group of viral hemorrhagic fevers characterized by a febrile syndrome and high case-fatality rates (1). LF differs from most viral hemorrhagic fevers in that it is endemic to a large geographic area of sub-Saharan Africa. Human cases of LF have been reported in (or imported from) Guinea, Sierra Leone, Liberia, Mali, Burkina Faso, and Nigeria; however, LF outbreaks seem to be restricted to Guinea, Sierra Leone, Liberia (the Mano River Union region), and Nigeria (2–4). In some areas of Sierra Leone and Guinea, more than half of the population has antibodies against Lassa virus (LASV; family Arenaviridae), the etiologic agent of LF (5,6). According to various estimates, 300,000–500,000 cases of LF result in 5,000–10,000 deaths annually in West Africa (6,7). An analysis based on seroepidemiologic data suggested that the number of cases might be much higher, reaching 3 million cases and 67,000 fatalities per year (8). Overall, the population at risk might include as many as 200 million persons living in a large swath of West Africa from Senegal to Nigeria and beyond (4).
LASV can cause infection in the multimammate rat (Mastomys natalensis), a natural host and reservoir of this pathogen (9,10). The multimammate rat is a commensal rodent ubiquitous in Africa (11,12). Although the routes of LASV infection are poorly characterized, humans probably get infected by eating contaminated food (13), by inhaling virus-contaminated aerosols (14), or while butchering infected rat meat (15). Person-to-person transmission of LASV is well documented, mostly in the form of nosocomial outbreaks (13).
Like other arenaviruses, LASV is an enveloped virus with a bisegmented single-stranded RNA genome encoding 4 proteins using an ambisense coding strategy (16). The small segment contains genes for the glycoprotein precursor (GPC) and nucleoprotein (NP), which serves as the main viral capsid protein. The large segment encodes the small zinc-binding protein (Z), which contains a RING motif, and another gene (L) containing the RNA-dependent RNA polymerase domain.
Complete genome sequences are available for several LASV strains, as are a considerable number of partial sequences from isolates originating from humans and rodents (17–20). Their analysis revealed the existence of high sequence diversity (up to 27% nt) and 4 major lineages of LASV, which correlate with geographic location (17). Lineages I, II, and III, and the greatest diversity of LASV strains, were found among isolates from Nigeria, whereas strains from Guinea, Sierra Leone, and Liberia seemed to be more closely related and belong exclusively to lineage IV. Sequence of the AV strain (21) and recently published sequences from rodent LASV isolates from Mali (18) suggest the existence of an additional clade (proposed as lineage V) (22). LASV sequences of isolates from humans and rodents are found interspersed throughout the phylogenetic tree, which is consistent with the notion that human cases typically result from transmission from rodents (17).
The high degree of sequence divergence of LASV genomes is a major problem affecting the development of molecular and immune-based diagnostic technologies, vaccines, and possibly antiviral drugs (13,16,17,23–25). Forty-seven unique partial LASV sequences from Sierra Leone were available in GenBank at the time of this analysis, which included fragments of NP (27 sequences), GPC (9 sequences), L (9 sequences), and Z (2 sequences) genes plus full sequences of small and large segments of 2 strains—Josiah and NL. Most of these sequences are from isolates collected >30 years ago; only 2 more recent sequences (GPC and L gene fragments) from strain SL06-2057 were isolated in 2006 (17,19).
To fill this gap, we investigated the sequence diversity of strains circulating among small rodents captured in peridomestic settings in Sierra Leone. In 2014, we screened 214 samples collected during 2009 from several species of rodents trapped in villages where LF was reported in humans. We used diagnostic reverse transcription PCR (RT-PCR) and high-density resequencing microarrays to detect LASV and amplify fragments of NP, GPC, and L genes. The obtained amplicons were sequenced and compared with previously published sequences from Sierra Leone to obtain a more complete and updated picture of the strains circulating in this country.
Dr. Leski is a research biologist at the Center for Bio/Molecular Science and Engineering at the Naval Research Laboratory. His research interests include the development and application of molecular diagnostics for pathogen detection and tracking the spread of antimicrobial resistance determinants in bacterial pathogens.
We thank Benjamin Kirkup and Zheng Wang for their critical evaluation of this manuscript.
Funding for this project was provided by the Office of Naval Research. M.P. was a Science and Engineering Apprenticeship Program (SEAP) summer intern supported by the American Society for Engineering Education as part of the Office of Naval Research, SEAP, at the Naval Research Laboratory.
- Frame JD, Baldwin JM Jr, Gocke DJ, Troup JM. Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. Am J Trop Med Hyg. 1970;19:670–6 .PubMed
- Sogoba N, Feldmann H, Safronetz D. Lassa fever in West Africa: evidence for an expanded region of endemicity. Zoonoses Public Health.2012;59(Suppl 2):43–7 . DOIPubMed
- Macher AM, Wolfe MS. Historical Lassa fever reports and 30-year clinical update. Emerg Infect Dis. 2006;12:835–7 . DOIPubMed
- Fichet-Calvet E, Rogers DJ. Risk maps of Lassa fever in West Africa. PLoS Negl Trop Dis. 2009;3:e388 . DOIPubMed
- Lukashevich IS, Clegg JC, Sidibe K. Lassa virus activity in Guinea: distribution of human antiviral antibody defined using enzyme-linked immunosorbent assay with recombinant antigen. J Med Virol. 1993;40:210–7 . DOIPubMed
- McCormick JB, Webb PA, Krebs JW, Johnson KM, Smith ES. A prospective study of the epidemiology and ecology of Lassa fever. J Infect Dis.1987;155:437–44 . DOIPubMed
- McCormick JB. Lassa fever. In: Saluzzo JF, Dodet B, editors. Emergence and control of rodent-borne viral diseases. Amsterdam: Elsevier; 1999. p. 177–95.
- Richmond JK, Baglole DJ. Lassa fever: epidemiology, clinical features, and social consequences. BMJ. 2003;327:1271–5 . DOIPubMed
- Monath TP, Newhouse VF, Kemp GE, Setzer HW, Cacciapuoti A. Lassa virus isolation from Mastomys natalensis rodents during an epidemic in Sierra Leone. Science. 1974;185:263–5 . DOIPubMed
- Walker DH, Wulff H, Lange JV, Murphy FA. Comparative pathology of Lassa virus infection in monkeys, guinea-pigs, and Mastomys natalensis. Bull World Health Organ. 1975;52:523–34 .PubMed
- Smit A, van der Bank H, Falk T, de Castro A. Biochemical genetic markers to identify two morphologically similar South African Mastomys species (Rodentia: Muridae). Biochem Syst Ecol. 2001;29:21–30 . DOIPubMed
- Rosevear DR. Muridae: typical rats & mice, wood mice, fat mice, swamp rats. In: Rosevear DR, editor. Rodents of West Africa. London: Trustees of the British Museum (Natural History); 1969. p. 227–496.
- Günther S, Lenz O. Lassa virus. Crit Rev Clin Lab Sci. 2004;41:339–90 . DOIPubMed
- Peters CJ, Jahrling PB, Liu CT, Kenyon RH, McKee KT Jr, Barrera Oro JG. Experimental studies of arenaviral hemorrhagic fevers. Curr Top Microbiol Immunol. 1987;134:5–68 . DOIPubMed
- Ter Meulen J, Lukashevich I, Sidibe K, Inapogui A, Marx M, Dorlemann A, Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea. Am J Trop Med Hyg. 1996;55:661–6 .PubMed
- Lukashevich I, Salvato MS. Lassa virus genome. Curr Genomics. 2006;7:351–79. DOI
- Bowen MD, Rollin PE, Ksiazek TG, Hustad HL, Bausch DG, Demby AH, Genetic diversity among Lassa virus strains. J Virol. 2000;74:6992–7004 .DOIPubMed
- Safronetz D, Sogoba N, Lopez JE, Maiga O, Dahlstrom E, Zivcec M, Geographic distribution and genetic characterization of Lassa virus in sub-Saharan Mali. PLoS Negl Trop Dis. 2013;7:e2582 . DOIPubMed
- Ehichioya DU, Hass M, Becker-Ziaja B, Ehimuan J, Asogun DA, Fichet-Calvet E, Current molecular epidemiology of Lassa virus in Nigeria. J Clin Microbiol. 2011;49:1157–61 . DOIPubMed
- Lecompte E, Fichet-Calvet E, Daffis S, Koulemou K, Sylla O, Kourouma F, Mastomys natalensis and Lassa fever, West Africa. Emerg Infect Dis.2006;12:1971–4 . DOIPubMed
- Günther S, Emmerich P, Laue T, Kuhle O, Asper M, Jung A, Imported Lassa fever in Germany: molecular characterization of a new Lassa virus strain.Emerg Infect Dis. 2000;6:466–76 . DOIPubMed
- Günther S, Weisner B, Roth A, Grewing T, Asper M, Drosten C, Lassa fever encephalopathy: Lassa virus in cerebrospinal fluid but not in serum. J Infect Dis. 2001;184:345–9 . DOIPubMed
- Trappier SG, Conaty AL, Farrar BB, Auperin DD, McCormick JB, Fisher-Hoch SP. Evaluation of the polymerase chain reaction for diagnosis of Lassa virus infection. Am J Trop Med Hyg. 1993;49:214–21 .PubMed
- Olschläger S, Lelke M, Emmerich P, Panning M, Drosten C, Hass M, Improved detection of Lassa virus by reverse transcription–PCR targeting the 5′ region of S RNA. J Clin Microbiol. 2010;48:2009–13 . DOIPubMed
- Demby AH, Chamberlain J, Brown DW, Clegg CS. Early diagnosis of Lassa fever by reverse transcription–PCR. J Clin Microbiol. 1994;32:2898–903.PubMed
- Mills JN, Childs JE, Ksiazek TG, Peters CJ, Wallis MV. Methods for trapping and sampling small mammals for virologic testing. Atlanta: US Department of Health and Human Services; 1995.
- Lecompte E, Brouat C, Duplantier J-M, Galan M, Granjon L, Loiseau A, Molecular identification of four cryptic species of Mastomys (Rodentia, Murinae). Biochem Syst Ecol. 2005;33:681–9. DOI
- Vieth S, Drosten C, Lenz O, Vincent M, Omilabu S, Hass M, RT-PCR assay for detection of Lassa virus and related Old World arenaviruses targeting the L gene. Trans R Soc Trop Med Hyg. 2007;101:1253–64 . DOIPubMed
- Leski TA, Lin B, Malanoski AP, Wang Z, Long NC, Meador CE, Testing and validation of high density resequencing microarray for broad range biothreat agents detection. PLoS ONE. 2009;4:e6569 . DOIPubMed
- Metzgar D, Myers CA, Russell KL, Faix D, Blair PJ, Brown J, Single assay for simultaneous detection and differential identification of human and avian influenza virus types, subtypes, and emergent variants. PLoS ONE. 2010;5:e8995 . DOIPubMed
- Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9 .DOIPubMed
- Huelsenbeck JP, Ronquist F. MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics. 2001;17:754–5 . DOIPubMed
- Vieth S, Torda AE, Asper M, Schmitz H, Gunther S. Sequence analysis of L RNA of Lassa virus. Virology. 2004;318:153–68 . DOIPubMed
- Lalis A, Leblois R, Lecompte E, Denys C, Ter Meulen J, Wirth T. The impact of human conflict on the genetics of Mastomys natalensis and Lassa virus in West Africa. PLoS ONE. 2012;7:e37068 . DOIPubMed
- ter Meulen J, Lenz O, Koivogui L, Magassouba N, Kaushik SK, Lewis R, Short communication: Lassa fever in Sierra Leone: UN peacekeepers are at risk. Trop Med Int Health. 2001;6:83–4 . DOIPubMed
- Shaffer JG, Grant DS, Schieffelin JS, Boisen ML, Goba A, Hartnett JN, Lassa fever in post-conflict Sierra Leone. PLoS Negl Trop Dis. 2014;8:e2748 .DOIPubMed
Suggested citation for this article: Leski TA, Stockelman MG, Moses LM, Park M, Stenger DA, Ansumana R, et al. Sequence variability and geographic distribution of Lassa virus, Sierra Leone. Emerg Infect Dis [Internet]. 2015 Apr [date cited]. http://dx.doi.org/10.3201/eid2104.141469
1These authors contributed equally to this article.
No hay comentarios:
Publicar un comentario