Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

被引：65

作者：

Mavigner, Maud ^{[1
]}

Raper, Jessica ^{[2
]}

Kovacs-Balint, Zsofia ^{[2
]}

Gumber, Sanjeev ^{[2
]}

O'Neal, Justin T. ^{[3
]}

Bhaumik, Siddhartha K. ^{[1
]}

Zhang, Xiaodong ^{[2
]}

Habib, Jakob ^{[1
]}

Mattingly, Cameron ^{[1
]}

McDonald, Circe E. ^{[3
]}

Avanzato, Victoria ^{[1
]}

Burke, Mark W. ^{[4
]}

Magnani, Diogo M. ^{[5
]}

Bailey, Varian K. ^{[5
]}

Watkins, David I. ^{[5
]}

Vanderford, Thomas H. ^{[2
]}

Fair, Damien ^{[6
]}

Earl, Eric ^{[6
]}

Feczko, Eric ^{[6
]}

Styner, Martin ^{[7
]}

Jean, Sherrie M. ^{[2
]}

Cohen, Joyce K. ^{[2
]}

Silvestri, Guido ^{[2
,8
]}

Johnson, R. Paul ^{[2
]}

O'Connor, David H. ^{[9
]}

Wrammert, Jens ^{[1
]}

Suthar, Mehul S. ^{[1
,3
]}

Sanchez, Mar M. ^{[2
,10
]}

Alvarado, Maria C. ^{[2
,10
]}

Chahroudi, Ann ^{[1
,2
,11
]}

机构：

[1] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[2] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA

[3] Emory Vaccine Ctr, Atlanta, GA 30329 USA

[4] Howard Univ, Dept Physiol & Biophys, Washington, DC 20060 USA

[5] Univ Miami, Dept Pathol, Miami, FL 33146 USA

[6] Oregon Hlth & Sci Univ, Portland, OR 97239 USA

[7] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA

[8] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[9] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA

[10] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA

[11] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2018年 / 10卷 / 435期

关键词：

RECOGNITION MEMORY; NEONATAL AMYGDALA; NEUROIMAGING FINDINGS; PREFRONTAL CORTEX; RHESUS MACAQUES; SOCIAL-BEHAVIOR; MACACA-MULATTA; HIPPOCAMPUS; LESIONS; RESPONSES;

D O I：

10.1126/scitranslmed.aao6975

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

引用

页数：15