High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkeys

South American Zika virus (ZIKV) emerged as a novel enzootic pathogen linked with neonatal brain defects and acute neuropathies, its natural history characterised by a sylvatic transmission cycle with arboreal mosquitoes and African primates. Yet infectivity studies in New World primates indigenous to Zika-endemic regions including host range, susceptibility, replication dynamics, tissue tropism and virus persistence are currently lacking. New World species Callithrix jacchus (marmosets) and Saguinus labiatus (red-bellied tamarins) were highly susceptible to sub-cutaneous challenge with South American ZIKVPRVABC59 inducing rapid, high, acute viraemia in each species. Differences in acute phase vRNA in blood were highly statistically significant at day 3 between these New and two Old World species Macaca mulatta (rhesus macaque) and Macaca fascicularis (cynomolgus macaque), Mann-Whitney U testp=0.00058. Comparative quantitative RT-PCR and RNAscope in situ hybridisation analysis of tissue viral copy number and cellular localisation patterns with Old World NHP revealed early, widespread distribution across multiple skin biopsies distant to the inoculation site, lymphoid organs, reproductive sites and the brain. While viraemia was cleared from blood by day 42 in all individuals, ZIKV persistence in most tissues was identified 100 days post-inoculation. Early neuroinvasion and persistence, following acutely resolved infection characterises ZIKV susceptibility in multiple hosts, especially New World species. Establishment of a ZIKV sylvatic cycle in the Americas may provide persistent animal reservoirs for future outbreak resurgence. New World monkeys represent viable models to understand ZIKV pathogenesis, potential therapeutic interventions and vaccine development strategies.