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Generation of reassortants between African arenaviruses
1Department of Special Pathogens, Byelorussian Research Institute of Epidemiology and Microbiology, Minsk, USSR.
Abstract:
Lassa (LAS) and Mopeia (MOP) viruses are African arenaviruses which are carried by wild rodents and occasionally transferred to humans. In humans and nonhuman primates, Lassa causes mortality in 60% of untreated cases, whereas Mopeia does not cause mortality and has been known to protect monkeys from lethal challenge with Lassa. These two African arenaviruses also differ in their lethality for suckling outbred mice and in their plaque sizes under agar overlay. MOP virus induces small plaques and lethal infection after intracerebral (ic) inoculation. In contrast, LAS inoculation does not kill mice and the virus induces large plaques. After coinfection of Vero cells with LAS and MOP viruses some phenotypic reassortants which produced small plaques and were not lethal for outbred mice were isolated and plaque-purified. Dot-blot hybridization using LAS and MOP cDNA probes specific for L and S RNA segments revealed a genotype consisting of the L RNA of MOP and the S RNA of LAS (MOP/LAS reassortant). Adoptive transfer experiments demonstrated an ability of immune splenocytes from CBA mice intraperitoneally infected with the MOP/LAS reassortants to protect recipient mice against lethal disease after ic inoculation with LAS virus.
Insights
Researchers created a novel Lassa virus reassortant (Mopeia/Lassa) from African arenaviruses. This reassortant is non-lethal in mice and protects against lethal Lassa virus infection, offering potential therapeutic insights.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Lassa virus (LAS) is a deadly African arenavirus, while Mopeia virus (MOP) is non-pathogenic and offers protection against LAS.
- Understanding the genetic basis of LAS pathogenicity and MOP's protective properties is crucial for developing interventions.
Purpose of the Study:
- To investigate the genetic determinants of LAS pathogenicity and MOP's protective immunity.
- To generate and characterize reassortant viruses with altered pathogenic and protective properties.
Main Methods:
- Coinfection of Vero cells with LAS and MOP viruses to generate reassortants.
- Plaque assays to assess viral characteristics (size, lethality).
- Dot-blot hybridization using specific cDNA probes to determine RNA segment composition (L and S segments).
- Adoptive transfer of immune splenocytes to evaluate protection against LAS challenge.
Main Results:
- Phenotypic reassortants with small plaques and non-lethal properties were isolated.
- A specific reassortant (MOP/LAS) was identified with the L RNA segment from MOP and the S RNA segment from LAS.
- Immune splenocytes from mice infected with the MOP/LAS reassortant conferred protection against lethal LAS virus challenge.
Conclusions:
- The MOP/LAS reassortant, carrying MOP's L RNA and LAS's S RNA, exhibits reduced pathogenicity.
- This reassortant demonstrates potential as a live-attenuated vaccine candidate or a tool for studying arenavirus immunity.
- Genetic reassortment can be a strategy to attenuate virulent viruses like Lassa, offering protective immunity.