Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques

Jessica Raper; Zsofia Kovacs-Balint; Maud Mavigner; Sanjeev Gumber; Mark W. Burke; Jakob Habib; Cameron Mattingly; Damien Fair; Eric Earl; Eric Feczko; Martin Styner; Sherrie M. Jean; Joyce K. Cohen; Mehul S. Suthar; Mar M. Sanchez; Maria C. Alvarado; Ann Chahroudi

doi:10.1038/s41467-020-16320-7

Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques

Jessica Raper, Zsofia Kovacs-Balint, Maud Mavigner, Sanjeev Gumber, Mark W. Burke, Jakob Habib, Cameron Mattingly, Damien Fair, Eric Earl, Eric Feczko, Martin Styner, Sherrie M. Jean, Joyce K. Cohen, Mehul S. Suthar, Mar M. Sanchez, Maria C. Alvarado, Ann Chahroudi

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.

Original language	English (US)
Article number	2534
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16320-7
State	Published - May 21 2020
Externally published	Yes

Bibliographical note

Funding Information:
The authors would like to thank Stephanie Ehnert and the YNPRC Division of Research Resources for expert assistance with animal procedures and Shanice Wilson, B.S. for her assistance with social behavior assessments. Funding for this study was provided by the Pilot Grant Program of the Yerkes National Primate Research Center, which is supported by the National Institutes of Health’s Office of the Director, Office of Research Infrastructures Programs, P51 OD011132, and the Center for Childhood Infections and Vaccines of Emory University and Children’s Healthcare of Atlanta (to A.C.).

Publisher Copyright:
© 2020, The Author(s).

Keywords

Animals
Brain/diagnostic imaging
Cognition/physiology
Disease Models, Animal
Female
Macaca mulatta
Memory/physiology
Nerve Net/diagnostic imaging
Neuroimaging
Social Behavior
Zika Virus/physiology
Zika Virus Infection/diagnostic imaging

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-020-16320-7

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Raper, J., Kovacs-Balint, Z., Mavigner, M., Gumber, S., Burke, M. W., Habib, J., Mattingly, C., Fair, D., Earl, E., Feczko, E., Styner, M., Jean, S. M., Cohen, J. K., Suthar, M. S., Sanchez, M. M., Alvarado, M. C., & Chahroudi, A. (2020). Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques. Nature communications, 11(1), Article 2534. https://doi.org/10.1038/s41467-020-16320-7

Raper, J, Kovacs-Balint, Z, Mavigner, M, Gumber, S, Burke, MW, Habib, J, Mattingly, C, Fair, D, Earl, E, Feczko, E, Styner, M, Jean, SM, Cohen, JK, Suthar, MS, Sanchez, MM, Alvarado, MC & Chahroudi, A 2020, 'Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques', Nature communications, vol. 11, no. 1, 2534. https://doi.org/10.1038/s41467-020-16320-7

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title = "Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques",

abstract = "Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.",

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author = "Jessica Raper and Zsofia Kovacs-Balint and Maud Mavigner and Sanjeev Gumber and Burke, {Mark W.} and Jakob Habib and Cameron Mattingly and Damien Fair and Eric Earl and Eric Feczko and Martin Styner and Jean, {Sherrie M.} and Cohen, {Joyce K.} and Suthar, {Mehul S.} and Sanchez, {Mar M.} and Alvarado, {Maria C.} and Ann Chahroudi",

note = "Funding Information: The authors would like to thank Stephanie Ehnert and the YNPRC Division of Research Resources for expert assistance with animal procedures and Shanice Wilson, B.S. for her assistance with social behavior assessments. Funding for this study was provided by the Pilot Grant Program of the Yerkes National Primate Research Center, which is supported by the National Institutes of Health{\textquoteright}s Office of the Director, Office of Research Infrastructures Programs, P51 OD011132, and the Center for Childhood Infections and Vaccines of Emory University and Children{\textquoteright}s Healthcare of Atlanta (to A.C.). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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AU - Kovacs-Balint, Zsofia

AU - Mavigner, Maud

AU - Gumber, Sanjeev

AU - Burke, Mark W.

AU - Habib, Jakob

AU - Mattingly, Cameron

AU - Fair, Damien

AU - Earl, Eric

AU - Feczko, Eric

AU - Styner, Martin

AU - Jean, Sherrie M.

AU - Cohen, Joyce K.

AU - Suthar, Mehul S.

AU - Sanchez, Mar M.

AU - Alvarado, Maria C.

AU - Chahroudi, Ann

N1 - Funding Information: The authors would like to thank Stephanie Ehnert and the YNPRC Division of Research Resources for expert assistance with animal procedures and Shanice Wilson, B.S. for her assistance with social behavior assessments. Funding for this study was provided by the Pilot Grant Program of the Yerkes National Primate Research Center, which is supported by the National Institutes of Health’s Office of the Director, Office of Research Infrastructures Programs, P51 OD011132, and the Center for Childhood Infections and Vaccines of Emory University and Children’s Healthcare of Atlanta (to A.C.). Publisher Copyright: © 2020, The Author(s).

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N2 - Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.

AB - Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.

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KW - Disease Models, Animal

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KW - Nerve Net/diagnostic imaging

KW - Neuroimaging

KW - Social Behavior

KW - Zika Virus/physiology

KW - Zika Virus Infection/diagnostic imaging

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ER -

Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

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