Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques

被引：0

作者：

Diogo M. Magnani

Thomas F. Rogers

Nicholas J. Maness

Nathan D. Grubaugh

Nathan Beutler

Varian K. Bailey

Lucas Gonzalez-Nieto

Martin J. Gutman

Núria Pedreño-Lopez

Jaclyn M. Kwal

Michael J. Ricciardi

Tereance A. Myers

Justin G. Julander

Rudolf P. Bohm

Margaret H. Gilbert

Faith Schiro

Pyone P. Aye

Robert V. Blair

Mauricio A. Martins

Kathrine P. Falkenstein

Amitinder Kaur

Christine L. Curry

Esper G. Kallas

Ronald C. Desrosiers

Pascal J. Goldschmidt-Clermont

Stephen S. Whitehead

Kristian G. Andersen

Myrna C. Bonaldo

Andrew A. Lackner

Antonito T. Panganiban

Dennis R. Burton

David I. Watkins

机构：

[1] University of Miami Leonard M. Miller School of Medicine,Department of Pathology

[2] The Scripps Research Institute,Department of Immunology and Microbiology

[3] Tulane National Primate Research Center,Institute for Antiviral Research

[4] Utah State University,Department of Obstetrics and Gynecology

[5] University of Miami Leonard M. Miller School of Medicine,Division of Clinical Immunology and Allergy, School of Medicine

[6] University of São Paulo,Department of Medicine

[7] University of Miami Leonard M. Miller School of Medicine,Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases

[8] National Institutes of Health,Department of Integrative Structural and Computational Biology

[9] Scripps Translational Science Institute,Laboratório de Biologia Molecular de Flavivírus

[10] The Scripps Research Institute,Ragon Institute

[11] Instituto Oswaldo Cruz,undefined

[12] Fiocruz,undefined

[13] Harvard Medical School,undefined

来源：

Nature Communications | / 9卷

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摘要：

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

引用

共 42 条

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