Zika viral dynamics and shedding in rhesus and cynomolgus macaques

Christa E. Osuna, So Yon Lim, Claire Deleage, Bryan D. Griffin, Derek Stein, Lukas T. Schroeder, Robert Omange, Katharine Best, Ma Luo, Peter T. Hraber, Hanne Andersen-Elyard, Erwing Fabian Cardozo Ojeda, Scott Huang, Dana L. Vanlandingham, Stephen Higgs, Alan S. Perelson, Jacob Estes, David Safronetz, Mark G. Lewis, James B. Whitney

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.

Original languageEnglish (US)
Pages (from-to)1448-1455
Number of pages8
JournalNature Medicine
Volume22
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Virus Shedding
Macaca mulatta
Viruses
Viral RNA
Blood
Saliva
Infection
Semen
Nervous System
Animals
Urine
Tissue
Cerebrospinal fluid
Plasmas
Viremia
Neurology
Adaptive Immunity
Virus Diseases
Innate Immunity
Cerebrospinal Fluid

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Osuna, C. E., Lim, S. Y., Deleage, C., Griffin, B. D., Stein, D., Schroeder, L. T., ... Whitney, J. B. (2016). Zika viral dynamics and shedding in rhesus and cynomolgus macaques. Nature Medicine, 22(12), 1448-1455. https://doi.org/10.1038/nm.4206

Zika viral dynamics and shedding in rhesus and cynomolgus macaques. / Osuna, Christa E.; Lim, So Yon; Deleage, Claire; Griffin, Bryan D.; Stein, Derek; Schroeder, Lukas T.; Omange, Robert; Best, Katharine; Luo, Ma; Hraber, Peter T.; Andersen-Elyard, Hanne; Ojeda, Erwing Fabian Cardozo; Huang, Scott; Vanlandingham, Dana L.; Higgs, Stephen; Perelson, Alan S.; Estes, Jacob; Safronetz, David; Lewis, Mark G.; Whitney, James B.

In: Nature Medicine, Vol. 22, No. 12, 01.12.2016, p. 1448-1455.

Research output: Contribution to journalArticle

Osuna, CE, Lim, SY, Deleage, C, Griffin, BD, Stein, D, Schroeder, LT, Omange, R, Best, K, Luo, M, Hraber, PT, Andersen-Elyard, H, Ojeda, EFC, Huang, S, Vanlandingham, DL, Higgs, S, Perelson, AS, Estes, J, Safronetz, D, Lewis, MG & Whitney, JB 2016, 'Zika viral dynamics and shedding in rhesus and cynomolgus macaques', Nature Medicine, vol. 22, no. 12, pp. 1448-1455. https://doi.org/10.1038/nm.4206
Osuna CE, Lim SY, Deleage C, Griffin BD, Stein D, Schroeder LT et al. Zika viral dynamics and shedding in rhesus and cynomolgus macaques. Nature Medicine. 2016 Dec 1;22(12):1448-1455. https://doi.org/10.1038/nm.4206
Osuna, Christa E. ; Lim, So Yon ; Deleage, Claire ; Griffin, Bryan D. ; Stein, Derek ; Schroeder, Lukas T. ; Omange, Robert ; Best, Katharine ; Luo, Ma ; Hraber, Peter T. ; Andersen-Elyard, Hanne ; Ojeda, Erwing Fabian Cardozo ; Huang, Scott ; Vanlandingham, Dana L. ; Higgs, Stephen ; Perelson, Alan S. ; Estes, Jacob ; Safronetz, David ; Lewis, Mark G. ; Whitney, James B. / Zika viral dynamics and shedding in rhesus and cynomolgus macaques. In: Nature Medicine. 2016 ; Vol. 22, No. 12. pp. 1448-1455.
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