Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses

Moshkoff, Dmitry; Salvato, María S.; Lukashevich, Igor S.

doi:10.1007/s11262-006-0050-3

Cited by 29 publications

(40 citation statements)

References 20 publications

(19 reference statements)

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“…As it has been shown for bunyaviruses, perfect complementarity within the 3' and 5' UTRs is required for maximal RNA replication [200]. It can not be rule out that these mutations additionally contributed to the attenuated phenotype of the ML29 reassortant [31,190]. As seen in Fig.…”

Section: Rna and Encoding Proteinsmentioning

confidence: 75%

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Lassa Virus Genome

Igor¹,

Sica²

2006

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Lassa virus (LASV), the most dangerous human pathogen among the Arenaviridae, belongs to a complex of genetically related virus strains responsible for the deaths of thousands of people in West Africa each year. The virus has a bi-segmented (L and S) single-stranded RNA genome. Each segment contains two genes in ambisense orientation. The L RNA encodes a large protein, L, or RdRp and a small zinc-binding, Z protein. The S RNA encodes the major structural proteins, nucleoprotein (NP) and glycoprotein precursor (GPC), cleaved into signal peptide, GP1, and GP2 glycoproteins. Genetic diversity among LASV strains is the highest within the family Arenaviridae and NP and RdRp genes are the most variable among LASV genes. The LASV genetic diversity is a great challenge for vaccine development.In addition to LASV and the prototype lymphocytic choriomeningitis virus (LCMV), the Old World group of arenaviruses includes three other related viruses, Mopeia (MOPV), Mobala (MOBV), and Ippy (IPPYV). These viruses as well as a MOP/LAS reassortant carrying the L RNA segment from MOPV and S RNA segment from LASV are non-pathogenic for experimental animals and are able to induce protective immunity against LASV. Lassa Fever pathogenesis is a sum of the effects induced by viral replication and immune response. The goal of this review is to cover recent publications on viral and host genes that control LASV virulence. The full-length genome sequence of LASV isolates and LASV-related nonpathogenic arenaviruses will provide a useful genetic tool to map LASV genes involved in virulence and to gain insight into phylogeny and evolution of the Old World arenaviruses.

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Section: Rna and Encoding Proteinsmentioning

confidence: 75%

“…(14)). Substitution Lys to Glu introduces two negatively charged R groups in positions 272-273 (Asp-Glu) distinguishing the MOP/LAS reassortant from other LASV strains so far analyzed [31,190].…”

Section: The Gp2 and Membrane Fusionmentioning

confidence: 99%

Lassa Virus Genome

Igor¹,

Sica²

2006

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“…This method allowed the detection and characterization of single-nucleotide variants and the evaluation of their frequency in each viral preparation. The sequences obtained from animal samples, viral stock (IGS-15), ML29-purified viral stock (IGS-27), and ML29 isolated after 12 passages in vitro (IGS-15) were compared with the published ML29 sequences (16). Each passage represents 48 h of infection at an MOI of 0.01.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, none of the major changes observed were reversions to wild-type parental virus (MOPV or LASV) sequences, and none of CAA, or 5=-L segment-ACAAGTTGGAGGGAACAGGGACT), dNTPs, and Platinum Taq DNA polymerase High Fidelity (Invitrogen) in 50-l reaction mixtures. The amplified products (L segment, approximately 7.4 kb, and S segment, 3.4 kb) were separated in Tris-borate-EDTA (TBE)-agarose gels and purified using a QIAquick Gel Extraction Kit (Qiagen), and each DNA strand was sequenced using a primer-walking method (1,16,17). All sequencing reactions were performed in the Applied Biosystems 3130xl automated sequencer using BigDye terminators (Applied Biosystems), and the sequences were edited and assembled using Sequencher v4.6 (Gene Codes Corporation, Ann Arbor, MI).…”

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confidence: 99%

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

Zapata

Goicochea

Nadai

et al. 2014

J Virol

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The attenuated Lassa vaccine candidate ML29 is a laboratory-produced reassortant between Lassa and Mopeia viruses, two Old World arenaviruses that differ by 40% in nucleic acid sequence. In our previous studies, ML29 elicited sterilizing immunity against Lassa virus challenge in guinea pigs and marmosets and virus-specific cell-mediated immunity in both simian immunodeficiency virus (SIV)-infected and uninfected rhesus macaques. Here, we show that ML29 is stable after 12 passages in vitro without losing its plaque morphology or its attenuated phenotype in suckling mice. Additionally, we used deep sequencing to characterize the viral population comprising the original stock of ML29, the stock of ML29 after 12 passages in Vero cells, and the ML29 isolates obtained from vaccinated animals. Twenty-seven isolates bore approximately 77 mutations that exceeded 20% of the single-nucleotide polymorphism (SNP) changes at any single locus. Of these 77 mutations, 5 appeared to be host specific, for example, appearing in mice but not in primates. None of these mutations were reversions of ML29 to the sequences of the parental Lassa and Mopeia viruses. The host-specific mutations indicate viral adaptations to virus-host interactions, and such interactions make reasonable targets for antiviral approaches. Variants capable of chronic infection did not emerge from any of the primate infections, even in immune-deficient animals, indicating that the ML29 reassortant is reasonably stable in vivo. In conclusion, the preclinical studies of ML29 as a Lassa virus vaccine candidate have been advanced, showing high levels of protection in nonhuman primates and acceptable stability both in vitro and in vivo.

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“…Several studies have been used to identify the protective capacity of this reassortant virus on LASV challenges [84,85,87,91]. ML-29 is capable of protecting against several strains of LASV, and shows potential to have some cross-protective tendencies for LCMV-WE [87].…”

Section: Future Directionsmentioning

confidence: 99%

The involvement of epithelial cells in arenavirus-induced pathogenesis.

Warner¹

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Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses

Cited by 29 publications

References 20 publications

Lassa Virus Genome

Lassa Virus Genome

Genetic Variation In Vitro and In Vivo of an Attenuated Lassa Vaccine Candidate

The involvement of epithelial cells in arenavirus-induced pathogenesis.

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