Dear Colleagues,

The Flavivirus genus, within the family Flaviviridae, includes over 50 arthropod-borne viruses, so called arboviruses. Yellow fever, after which the genus is named, was the first virus demonstrated to cause an arthropod-borne disease. Additional important human pathogens, including the four dengue viruses (DENV), Japanese encephalitis (JEV), West Nile (WNV), Zika (ZIKV), and tick-borne encephalitis viruses, belong to the genus.  Importantly, zoonotic flaviviruses constitutes one of the main challenges for human and animal health. DENV cause around 21.000 human deaths annually, and it is estimated that at least 120 countries have endemic Dengue viruses transmission; ZIKV was recently responsible in affected areas for microcephaly and other severe brain defects following infections of pregnant women. WNV has become more prominent as a zoonotic agent, particularly in Europe and North America, where infections in humans, horses and birds have been reported. Human infected with WNV may develop a mild flu-like illness consisting of symptoms such as malaise, eye pain, headache, myalgia, gastrointestinal discomfort, and rash. However, 1% of persons with clinical illness may develop neuroinvasive disease such as meningitis, encephalitis, and acute flaccid paralysis

USUV was discovered in 1959 from a mosquito of the Culex neavei species in South Africa and isolated by intracerebral inoculation of newborne mice. The natural life cycle of USUV is similar to WNV: it involves birds as reservoirs and ornithophilic mosquitoes as vectors like the common Culex pipiens. USUV was considered for decades as a flavivirus with low zoonotic potential. However, recent data from various European countries indicate that there also might be a much higher number of clinical neuro-invasive USUV infections in humans than assumed to date. As WNV, USUV circulates in multiple genetic lineages and according to recent surveillance studies, WNV and USUV are the most widespread mosquito-borne flaviviruses in Europe, with co-circulation in the same geographical areas.

Although over the last years some breakthroughs have been achieved, there are important gaps of knowledge regarding the pathogenesis and immunological mechanisms of USUV. In this perspective, knowledge regarding the interaction of pre-exisiting flavivirus immunity and USUV infection, or vice versa, is also lacking.   

In this issue, we would like to focus on all aspects of USUV that provide an update of our current knowledge of the disease and of the interaction of USUV with extant flaviviruses. Topics of interest include (but are not limited to) epidemiology, transmission pathways, vector competence, host–virus interactions, mechanisms of infection and viral spread, cell-virus interactions, disease dynamics, clinical aspects, pathology and standardization of pathological evaluation protocols, disease pathogenesis, factors responsible for virus virulence, virus persistence, immune responses correlated with protection and how these can be activated, and development and improvement of diagnostic techniques.

Dr. Alessio Lorusso
Dr. Giovanni Savini
Guest Editors

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• Usutu virus
• USUV
• flavivirus
• epidemiology
• pathogenesis
• cell-virus interaction
• pre-existing immunity
• pathology
• vectors
• diagnosis
• molecular epidemiology
• clinical aspects
• immune response
• experimental models of infection