TY - JOUR
T1 - Evolution of ocular defects in infant macaques following in utero Zika virus infection
AU - Yiu, Glenn
AU - Thomasy, Sara M.
AU - Isabel Casanova, M.
AU - Rusakevich, Alexander
AU - Keesler, Rebekah I.
AU - Watanabe, Jennifer
AU - Usachenko, Jodie
AU - Singapuri, Anil
AU - Ball, Erin E.
AU - Bliss-Moreau, Eliza
AU - Guo, Wendi
AU - Webster, Helen
AU - Singh, Tulika
AU - Permar, Sallie
AU - Ardeshir, Amir
AU - Schneider Coffey, Lark L
AU - van Rompay, Koen K.A.
N1 - Funding Information:
We thank M. Allen, V. Bakula, M. Christensen, I. Cazares, W. von Morgenland, the veterinary staff, pathology staff, and the staff of Colony Management and Research Services, and Clinical Laboratory at the California National Primate Center for expert assistance. This study was supported by R21AI129479 (to KKAVR), the Office of Research Infrastructure Program/OD (P510D011107; CNPRC), and the large animal imaging core of NEI P30 EY12576. GY is supported by NIH K08 EY026101, NIH R21 EY031108, the BrightFocus Foundation, and Macula Society. SMT is supported by NIH U24 EY029904. Histological studies of the eyes were conducted at the Comparative Ocular Pathology Laboratory of Wisconsin. No funding organizations had any role in the design or conduct of this research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Publisher Copyright:
Copyright: © 2020, Yiu et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2020/12/17
Y1 - 2020/12/17
N2 - Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.
AB - Congenital Zika syndrome (CZS) is associated with microcephaly and various neurological, musculoskeletal, and ocular abnormalities, but the long-term pathogenesis and postnatal progression of ocular defects in infants are not well characterized. Rhesus macaques are superior to rodents as models of CZS because they are natural hosts of the virus and share similar immune and ocular characteristics, including blood–retinal barrier characteristics and the unique presence of a macula. Using a previously described model of CZS, we infected pregnant rhesus macaques with Zika virus (ZIKV) during the late first trimester and characterized postnatal ocular development and evolution of ocular defects in 2 infant macaques over 2 years. We found that one of them exhibited colobomatous chorioretinal atrophic lesions with macular and vascular dragging as well as retinal thinning caused by loss of retinal ganglion neuron and photoreceptor layers. Despite these congenital ocular malformations, axial elongation and retinal development in these infants progressed at normal rates compared with healthy animals. The ZIKV-exposed infants displayed a rapid loss of ZIKV-specific antibodies, suggesting the absence of viral replication after birth, and did not show any behavioral or neurological defects postnatally. Our findings suggest that ZIKV infection during early pregnancy can impact fetal retinal development and cause congenital ocular anomalies but does not appear to affect postnatal ocular growth.
UR - http://www.scopus.com/inward/record.url?scp=85097826106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097826106&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.143947
DO - 10.1172/jci.insight.143947
M3 - Article
C2 - 33180748
AN - SCOPUS:85097826106
VL - 5
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 24
M1 - e143947
ER -