Prospective investigation of oxidative stress in West Nile virus infection

WNV infection is the most common cause of epidemic encephalitis in humans in Europe and the
United States. West Nile Neuro-invasive Disease (WNND) develops in 1% of infected individuals; it has
a 10% case fatality rate and is associated with long-term neurologic and cognitive sequelae in
survivors. WNV penetrates the blood-brain barrier, invades the central nervous system and causes
necrosis and apoptosis of neurons, but the extent of neuronal injury encountered in brain regions with
similar viral load varies widely. We hypothesize that the induction of oxidative stress and autophagy
by WNV infection determines the severity of infection and the outcome of neuronal injury in WNV
infection. During the 2020 WNV transmission season in Romania, one of the high burden countries in
Europe, we will for the first time, comprehensively investigate the sequential intra-host profile of a
panel of established markers of oxidative stress and autophagy in plasma, erythrocytes, Peripheral
Blood Mononuclear Cells, serum and urine in human WNV cases (n=10) and age-matched healthy
controls (n=5). We will develop multiparameter indexes to measure the redox status and to
investigate associations of these indexes with clinical, radiological and neuropsychological outcomes.
Elucidation of the role of oxidative stress could lead to new opportunities for pharmacotherapeutic
interventions in WNV infections.