TY - JOUR T1 - A rhesus macaque model of Asia lineage Zika virus infection JF - bioRxiv DO - 10.1101/046334 SP - 046334 AU - Dawn M. Dudley AU - Matthew T. Aliota AU - Emma Mohr AU - Andrea M. Weiler AU - Gabrielle Lehrer-Brey AU - Kim L. Weisgrau AU - Mariel S. Mohns AU - Meghan E. Breitbach AU - Mustafa N. Rasheed AU - Christina M. Newman AU - Dane D. Gellerup AU - Louise H. Moncla AU - Jennifer Post AU - Nancy Schultz-Darken AU - Michele L. Schotkzo AU - Jennifer M. Hayes AU - Josh A. Eudailey AU - M. Anthony Moody AU - Sallie R. Permar AU - Shelby L. O’Connor AU - Eva G. Rakasz AU - Heather A. Simmons AU - Saverio Capuano III AU - Thaddeus G. Golos AU - Jorge E. Osorio AU - Thomas C. Friedrich AU - David H. O’Connor Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/10/046334.abstract N2 - Infection with Asian lineage Zika virus has been associated with Guillain-Barré syndrome and fetal abnormalities 1–4, but the mechanisms and risk factors for these outcomes remain unknown. Here we show that rhesus macaques are susceptible to infection by an Asian-lineage virus closely related to strains currently circulating in the Americas. Following subcutaneous inoculation, Zika virus RNA was detected in plasma one day post-infection (dpi) in all animals (N = 8, including 2 animals infected during the first trimester of pregnancy). Plasma viral loads peaked above 1 × 105 viral RNA copies/mL in seven of eight animals. Viral RNA was also present in saliva, urine, and cerebrospinal fluid (CSF), consistent with case reports from infected humans. Viral RNA was cleared from plasma and urine by 21 dpi in non-pregnant animals. In contrast, both pregnant animals remained viremic longer, up to 57 days. In all animals, infection was associated with transient increases in proliferating natural killer cells, CD8+ T cells, CD4+ T cells, and plasmablasts. Neutralizing antibodies were detected in all animals by 21 dpi. Rechallenge of three non-pregnant animals with the Asian-lineage Zika virus 10 weeks after the initial challenge resulted in no detectable virus replication, suggesting that primary Zika virus infection elicits protective immunity against homologous virus strains. These data establish that Asian-lineage Zika virus infection of rhesus macaques provides a relevant animal model for studying pathogenesis in pregnant and non-pregnant individuals and evaluating potential interventions against human infection, including during pregnancy. ER -