Abstract
West Nile virus (WNV) is a mosquito-borne flavivirus that infects humans and other mammals. In some cases WNV causes severe neurological disease. During recent years, outbreaks of WNV are increasing in worldwide distribution and novel genetic variants of the virus have been detected. Although a substantial amount of data exists on WNV infections in rodent models, little is known about early events during WNV infection in primates, including humans. To gain a deeper understanding of this process, we performed experimental infections of rhesus macaques and common marmosets with a virulent European WNV strain (WNV-Ita09) and monitored virological, hematological, and biochemical parameters. WNV-Ita09 productively infected both monkey species, with higher replication and wider tissue distribution in common marmosets compared to rhesus macaques. The animals in this study however, did not develop clinical signs of WNV disease, nor showed substantial deviations in clinical laboratory parameters. In both species, the virus induced a rapid CD56dimCD16bright natural killer response, followed by IgM and IgG antibody responses. The results of this study show that healthy rhesus macaques and common marmosets are promising animal models to study WNV-Ita09 infection. Both models may be particularly of use to evaluate potential vaccine candidates or to investigate WNV pathogenesis.
Highlights
West Nile virus (WNV) is a mosquito-borne RNA virus within the Flavivirus genus
The number of WNV infections in Europe has increased in recent years and is caused by viruses that are genetically different from the viruses that caused the WNV epidemic in North America
We have experimentally infected two different monkey species, rhesus macaques and common marmosets, with the European WNV isolate Ita09 to evaluate the early events after infection and the onset of the disease
Summary
West Nile virus (WNV) is a mosquito-borne RNA virus within the Flavivirus genus. Mosquitos of the genus Culex are the most important insect vectors, but the virus can be transmitted by a wide variety of mosquitos from other genera [1]. The enzootic viral lifecycle is between mosquitos and bird species, but transmission can occur to other hosts, including horses and humans. The majority of infections (80%) are asymptomatic, and approximately 20% of the infected individuals develop a febrile syndrome, characterized by weakness, myalgia, and fatigue. In less than 1% of WNV-infected patients, illness progresses to a sometimes fatal, neuro-invasive form that results in meningitis, encephalitis, or paralysis. The elderly and immunocompromised are at substantially higher risk for severe WNV disease [2] compared to immunocompentent individuals
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