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Persistence of tick-borne encephalitis virus in monkeys. I. Features of experimental infection
Abstract:
Sixty-seven Macaca rhesus monkeys were inoculated with 2 mutants and 3 virulent strains of tick-borne encephalitis (TBE) virus including strains isolated from patients with a chronic form of TBE. A model of the clinical course of acute, subacute, and chronic encephalitis was produced by intracerebral inoculation and that of asymptomatic infection was produced by subcutaneous inoculation [with or without administration of cyclophosphane (CP)]. Virus persistence developed after inoculation with all the strains, after non-fatal encephalitis and inapparent infection irrespective of CP administration. In monkeys recovering from encephalitis the virus persisted for at least 783 days. After asymptomatic infection, it persisted for 302 days; neither virus nor virus-specific antigen was detected at 356, 367, and 620 days.
Insights
Tick-borne encephalitis (TBE) virus can persist in rhesus monkeys long-term after both symptomatic and asymptomatic infections. This study modeled TBE virus persistence in a primate model, revealing prolonged viral presence.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Tick-borne encephalitis (TBE) poses a significant public health threat, characterized by neurological complications.
- Understanding TBE virus persistence is crucial for developing effective treatment and prevention strategies.
- Previous studies have explored TBE virus pathogenesis, but long-term persistence models are less defined.
Purpose of the Study:
- To establish a primate model for studying the clinical course and viral persistence of tick-borne encephalitis (TBE) virus.
- To investigate the duration and patterns of TBE virus persistence following different inoculation routes and viral strains.
- To evaluate the impact of cyclophosphane (CP) on TBE virus persistence in a Macaca rhesus monkey model.
Main Methods:
- Sixty-seven Macaca rhesus monkeys were inoculated with five different TBE virus strains (2 mutants, 3 virulent).
- Intracerebral inoculation modeled acute, subacute, and chronic encephalitis; subcutaneous inoculation modeled asymptomatic infection, with or without cyclophosphane (CP).
- Virus persistence was monitored over extended periods post-inoculation.
Main Results:
- Virus persistence was observed in all inoculated monkeys, regardless of the TBE virus strain used.
- Following non-fatal encephalitis, the virus persisted for at least 783 days.
- In monkeys with asymptomatic infections, virus persisted for 302 days, with no detection at later time points (356, 367, 620 days).
Conclusions:
- The Macaca rhesus monkey model effectively replicates acute, subacute, chronic, and asymptomatic forms of TBE.
- TBE virus demonstrates prolonged persistence in primates after both clinical and subclinical infections.
- These findings highlight the potential for long-term viral reservoirs in TBE infection, irrespective of initial disease severity or immunosuppression.