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

作者：Maud Mavigner, Jessica Raper, Zsofia Kovacs‐Balint, Sanjeev Gumber, Justin T. O’Neal, Siddhartha Kumar Bhaumik, Xiaodong Zhang, Jakob Habib, Cameron Mattingly, Circe E. McDonald, Victoria A. Avanzato, Mark Burke, Diogo M. Magnani, Varian K. Bailey, David I. Watkins, Thomas H. Vanderford, Damien A. Fair, Eric Earl, Eric Feczko, Martin Styner, Sherrie Jean, Joyce K. Cohen, Guido Silvestri, R. Paul Johnson, David H. O’Connor, Jens Wrammert, Mehul S. Suthar, Mar M. Sánchez, Maria C. Alvarado, Ann Chahroudi · 发表于：Science Translational Medicine · 年份：2018 · DOI：10.1126/scitranslmed.aao6975 · 被引用次数：90 · 研究领域：Mosquito-borne diseases and control、Primate Behavior and Ecology、COVID-19 epidemiological studies

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 ped...