RT Journal Article SR Electronic T1 A rhesus macaque model of Asia lineage Zika virus infection JF bioRxiv FD Cold Spring Harbor Laboratory SP 046334 DO 10.1101/046334 A1 Dawn M. Dudley A1 Matthew T. Aliota A1 Emma Mohr A1 Andrea M. Weiler A1 Gabrielle Lehrer-Brey A1 Kim L. Weisgrau A1 Mariel S. Mohns A1 Meghan E. Breitbach A1 Mustafa N. Rasheed A1 Christina M. Newman A1 Dane D. Gellerup A1 Louise H. Moncla A1 Jennifer Post A1 Nancy Schultz-Darken A1 Michele L. Schotkzo A1 Jennifer M. Hayes A1 Josh A. Eudailey A1 M. Anthony Moody A1 Sallie R. Permar A1 Shelby L. O’Connor A1 Eva G. Rakasz A1 Heather A. Simmons A1 Saverio Capuano III A1 Thaddeus G. Golos A1 Jorge E. Osorio A1 Thomas C. Friedrich A1 David H. O’Connor YR 2016 UL http://biorxiv.org/content/early/2016/05/10/046334.abstract AB 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.