Differential pathogenesis of Usutu virus isolates in mice

Area of Science:

• Virology
• Epidemiology
• Pathogen emergence

Background:

• Usutu virus (USUV), a Flavivirus and relative of West Nile virus, is zoonotic and can cause human neuroinvasive disease.
• USUV circulates between Culex mosquitoes and birds, spreading across Africa and Europe since 1959.
• Human USUV cases have increased, particularly in Europe, with a spectrum of illness from mild to severe neurological effects.

Purpose of the Study:

• To investigate potential increases in Usutu virus pathogenicity during its emergence in Europe.
• To compare the virulence of historic and recent USUV isolates from Africa and Europe in a mouse model.

Main Methods:

• Inoculation of interferon-α/β receptor knockout (Ifnar1-/-) mice with USUV strains from South Africa, Africa, Spain, and the Netherlands.
• Assessment of mortality rates, survival times, histopathology, and viremia levels in infected mice.

Main Results:

• African strains and a Spanish USUV strain induced 100% mortality in mice, with comparable severity.
• A European strain from the Netherlands showed significantly lower mortality (12%) and reduced tissue pathology.
• Viremia was highest with recent African strains and lowest with the Netherlands strain, despite separate introductions into Europe.

Conclusions:

• USUV pathogenicity varies among strains circulating in Europe, with some exhibiting reduced virulence compared to African isolates.
• Separate introductions of USUV into Europe may lead to different disease outcomes.
• Virulent African USUV strains remain a significant public health concern, even with increased reported cases in Europe.