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Reduced virulence of a Junin virus mutant is associated with restricted multiplication in murine cells
L A Scolaro1, S E Mersich, E B Damonte
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Abstract:
C167, a mutant derived from the XJC13 strain of Junin virus, is highly attenuated in its pathogenic properties for newborn mice. Whereas 10(2).PFU of XJC13 injected intracerebrally killed 100% of two-day-old mice, the mutant showed no detectable lethality. Survival of mice infected with C167 was associated with a reduced and delayed virus replication in brain and a defective spread of virus from the site of inoculation to the other tissues, including spleen, kidney, thymus, liver, peritoneal cells and serum. As an apparent consequence of the restricted replication of C167 in mice, no detectable interferon induction and low levels of neutralizing antibodies were observed. Analysis of multiplication kinetics of C167 and XJC13 in different cell cultures in vitro has confirmed that the attenuated phenotype of C167 was related to a specific inefficient replication in murine cells. This host-range restriction was due to a combination of adsorption and penetration blockage.
Insights
Junin virus mutant C167 shows significantly reduced pathogenicity in newborn mice. This attenuated Junin virus exhibits inefficient replication in murine cells due to adsorption and penetration blockages.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Junin virus (JUNV) is a causative agent of Argentine hemorrhagic fever.
- JUNV strains exhibit varying degrees of virulence.
- Understanding viral attenuation mechanisms is crucial for vaccine development.
Purpose of the Study:
- To characterize the attenuation of Junin virus mutant C167.
- To elucidate the molecular basis for C167's reduced pathogenicity in mice.
- To investigate the host-range restriction of C167.
Main Methods:
- Intracerebral inoculation of newborn mice with wild-type XJC13 and mutant C167 strains.
- Assessment of viral replication and spread in various tissues.
- In vitro analysis of viral multiplication kinetics in cell cultures.
- Investigation of viral adsorption and penetration efficiency.
Main Results:
- Mutant C167 demonstrated no lethality in mice, unlike the virulent XJC13 strain.
- C167 exhibited reduced and delayed viral replication in the brain and impaired systemic spread.
- Inefficient replication of C167 in murine cells was observed in vitro.
- Host-range restriction was attributed to combined adsorption and penetration defects.
Conclusions:
- Junin virus mutant C167 is highly attenuated due to inefficient replication in murine cells.
- The attenuation phenotype is linked to specific defects in viral adsorption and penetration.
- These findings provide insights into JUNV host-pathogen interactions and attenuation mechanisms.