Inapparent Tick-Borne Orthoflavivirus Infection in Macaca fascicularis: A Model for Antiviral Drug and Vaccine Research

Abstract

Tick-borne encephalitis virus (TBEV) and Powassan virus (POWV) are neurotropic tick-borne orthoflaviviruses. They cause mostly asymptomatic infections in hosts, but severe forms with CNS involvement can occur. Studying the early stages of viral infections in humans is challenging, and appropriate animal models are essential for understanding the factors determining the disease severity and for developing emergency prophylaxis and treatment options. In this work, we assessed the model of the early stages of TBEV and POWV mono- and co-infections in Macaca fascicularis. Serological, biochemical, and virological parameters were investigated to describe the infection, including its impact on animal behavior. Viremia, neutralizing antibody dynamics, and viral load in organs were chosen as the main parameters distinguishing early-stage orthoflavivirus infection. Levels of IFNα, monocyte count, and cognitive test scores were proposed as additional informative indicators. An assessment of a tick-borne encephalitis vaccine using this model showed that it provided partial protection against POWV infection in Macaca fascicularis without signs of antibody-dependent enhancement of infection.

An Integrative Approach to the Study of Cognitive Abilities in a Non-Human Primate Model in a Virology Laboratory Environment

“…The scientific literature describes numerous cases of patients complaining about increased tiredness and inefficiency after suffering infections [23,28,29]. In our work, we demonstrated that the "Tiredness" test battery can be used to evaluate the efficiency and tiredness of primates.…”

“…Our test program was previously validated in work [23]. Using these tests, we were able to detect some cognitive impairment in primates with inapparent orthoflavivirus infections.…”

“…Previously, we conducted experiments to assess the impact of asymptomatic orthoflavivirus infection on the behavior and cognitive abilities of Macaca fascicularis [23]. Concurrently with the training of the primates, we conducted experiments to evaluate their cognitive capabilities, which were based on various cognitive functions, such as memory, attentional focus, spatial perception, and decision-making, and we encountered the situation that only a portion of the primates from the study group were ready to co-operate and were capable of performing intellectual tasks.…”