Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies

Best, Katharine; Guedj, Jeremie; Madelain, Vincent; de Lamballerie, Xavier; Lim, So-Yon; Osuna, Christa E.; Whitney, James B.; Perelson, Alan S.

doi:10.1073/pnas.1704011114

Zika plasma viral dynamics in nonhuman primates provides insights into early infection and antiviral strategies

Journal Article · Tue Aug 15 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1704011114· OSTI ID:1373602

Best, Katharine ^[1]; Guedj, Jeremie ^[2]; Madelain, Vincent ^[2]; de Lamballerie, Xavier ^[3]; Lim, So-Yon ^[4]; Osuna, Christa E. ^[4]; Whitney, James B. ^[5]; Perelson, Alan S. ^[1]

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,
Infection, Antimicrobials, Modelling, Evolution, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France,
UMR Emergence des Pathologies Virales, Aix-Marseille University, Institut de Recherche pour le Développement 190, INSERM 1207, École des Hautes Études en Santé Publique, F-13385 Marseille, France,, UMR “Emergence des Pathologies Virales,” Institut Hospitalo-Universitaire Méditerranée Infection, F-13385 Marseille, France,
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215,
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215,, Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139

Significance

In light of the recent outbreak of Zika virus (ZIKV), an understanding of the within-host viral dynamics is essential to assess persistence in vivo, transmission risk, and antiviral therapeutics. Using mathematical modeling we find that, in nonhuman primates, the viral dynamics of ZIKV are characterized by a short lifetime of infected cells (<10 h) during which enough viral particles are produced to infect ∼11 other cells. Higher disease burden is associated with changes in natural killer cell subset concentrations and with elevated expression of the cytokine MCP-1, although the mechanisms behind these associations remain unclear. In order for an antiviral treatment to effectively reduce the time to plasma viral clearance therapy should be initiated at the time of infection or given prophylactically.

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Research Organization:: Los Alamos National Laboratory (LANL)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC52-06NA25396

OSTI ID:: 1373602

Alternate ID(s):: OSTI ID: 1330177

Report Number(s):: LA-UR-16-28095

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 33 Vol. 114; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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