RT Journal Article
SR Electronic
T1 Experimental Zika Virus Infection in a New World Monkey Model Reproduces Key Features of the Human Disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 102145
DO 10.1101/102145
A1 Charles Chiu
A1 Jerome Bouquet
A1 Tony Li
A1 Shigeo Yagi
A1 Claudia Sanchez San Martin
A1 Manasi Tamhankar
A1 Vida L. Hodara
A1 Laura M. Parodi
A1 Sneha Somasekar
A1 Guixia Yu
A1 Luis D. Giavedoni
A1 Suzette Tardif
A1 Jean Patterson
YR 2017
UL http://biorxiv.org/content/early/2017/01/21/102145.abstract
AB 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 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, anduncovered 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.