Experimental Infection of Rhesus Macaques and Common Marmosets with a European Strain of West Nile Virus

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 CD56(dim)CD16(bright) 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. Author Summary West Nile virus (WNV) is a mosquito-borne virus that can infect mammals, including humans. Most infected humans do not develop disease, but in about 20% of cases humans develop WNV-related disease symptoms, varying in severity from fever to a sometimes life-threatening neuro-invasive disease. 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. In this study, 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. Both species were equally susceptible to infection with WNV-Ita09, but differences between species were observed. Compared to rhesus macaques, common marmosets had higher virus loads in blood, and presented a wider distribution of the virus in various organs. Based on the analysis of virological, immunological, biochemical and hematological parameters, we conclude that rhesus macaques as well as common marmosets are potentially useful animal models to evaluate vaccine candidates or to investigate WNV pathogenesis.