Experimental Zika Virus Infection in a New World Monkey Model Reproduces Key Features of the Human Disease [article]

Charles Y Chiu, Jerome Bouquet, Tony Li, Shigeo Yagi, Claudia Sanchez San Martin, Manasi Tamhankar, Vida L Hodara, Laura L Parodi, Sneha Somasekar, Guixia Yu, Luis D Giavedoni, Suzette Tardif (+1 others)
2017 bioRxiv   pre-print
Human infections by Zika virus (ZIKV), a mosquito-borne flavivirus, are associated with a current widespread outbreak in the Americas, and have been associated with neurological complications and adverse fetal outcomes such as microcephaly in pregnant women. A suitable non-human primate model is urgently needed. To evaluate ZIKV infectivity, pathogenesis, and persistence, we inoculated 4 marmosets with ZIKV and followed them by clinical monitoring and serial sampling of body fluids for up to 11
more » ... weeks. We found that marmosets experimentally infected with ZIKV reproduced key features of the human disease, including (1) asymptomatic infection, (2) brief period of detectable virus in serum (<1 week), (3) detection in other body fluids (urine, saliva, semen, and stool) for at least 2 weeks following acute infection, and (4) persistence in lymph nodes, but not other tissues, at 1 month post-infection. ZIKV-positive saliva and serum samples, but not urine, were found to be infectious in cell culture. By day 6 post-inoculation, most marmosets exhibited detectable neutralizing antibody responses concurrent with activation of NK cell and B cell subsets and an increase in circulating cytokines associated with type II interferon signaling, Transcriptome profiling revealed enrichment of immune responses to active viral infection, with up-regulation of both type I and II interferon signaling pathways, and uncovered potential host biomarkers. These results suggest that a New World monkey model of acute ZIKV infection mimics the human disease, and is likely to be useful for testing of drug and vaccine candidates.
doi:10.1101/102145 fatcat:fr5hzsx4tvfyjak3wg4vyn244i