151. Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques
- Author
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Dawn M. Dudley, David H. O’Connor, Thaddeus G. Golos, Leah C. Katzelnick, Terry K. Morgan, Eric Peterson, Elizabeth A. Brown, Andrea M. Weiler, Keisuke Yamamoto, Eva Harris, Chelsea M. Crooks, Anna S. Jaeger, Megan E. Murphy, Angel Balmaseda, Thomas C. Friedrich, Amber Possell, Sierra Rybarczyk, Katarina M. Braun, Jens C. Eickhoff, Kara Weaver, Heather A. Simmons, Christina M. Newman, Elaina Razo, Mason Bliss, Phoenix M. Shepherd, Nancy Schultz-Darken, Ann Mitzey, Kathleen M. Antony, Andres Mejia, Jennifer M. Hayes, Emma L. Mohr, Matthew T. Aliota, and Michael K. Fritsch
- Subjects
0301 basic medicine ,RNA viruses ,Viral Diseases ,Embryology ,Physiology ,viruses ,Placenta ,Maternal Health ,RC955-962 ,Dengue virus ,Monkeys ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Antibodies, Viral ,Virus Replication ,Macaque ,Biochemistry ,Zika virus ,Dengue ,0302 clinical medicine ,Medical Conditions ,Pregnancy ,Arctic medicine. Tropical medicine ,Immune Physiology ,Medicine and Health Sciences ,Medicine ,030212 general & internal medicine ,Antigens, Viral ,Maternal-Fetal Exchange ,Mammals ,Immune System Proteins ,biology ,Zika Virus Infection ,virus diseases ,Eukaryota ,Obstetrics and Gynecology ,Infectious Diseases ,Medical Microbiology ,Viral Pathogens ,Vertebrates ,Viruses ,RNA, Viral ,Female ,Antibody ,Public aspects of medicine ,RA1-1270 ,Pathogens ,Anatomy ,Viral load ,Research Article ,Primates ,Immunology ,Viremia ,Microbiology ,Antibodies ,03 medical and health sciences ,Immunity ,biology.animal ,Old World monkeys ,Animals ,Microbial Pathogens ,Biology and life sciences ,Flaviviruses ,business.industry ,Public Health, Environmental and Occupational Health ,Organisms ,Reproductive System ,Proteins ,Zika Virus ,biochemical phenomena, metabolism, and nutrition ,Dengue Virus ,biology.organism_classification ,medicine.disease ,Virology ,Infectious Disease Transmission, Vertical ,030104 developmental biology ,Viral replication ,Amniotes ,biology.protein ,Women's Health ,business ,Zoology ,Developmental Biology - Abstract
Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate., Author summary Zika virus (ZIKV) gained global attention during an explosive outbreak in the Americas in 2015–16 when it was causally associated with the constellation of birth defects now termed congenital Zika syndrome (CZS). However, a substantial proportion of gestational ZIKV infections result in babies without apparent birth defects. Could there be other factors that influence ZIKV pathogenicity? For example, it is well-established that pre-existing immunity to one dengue virus (DENV) serotype can enhance the severity of a secondary DENV infection. ZIKV is antigenically closely related to DENV, but whether DENV-specific antibodies enhance the severity of ZIKV infection is unclear. To answer this question, we used our non-human primate model of ZIKV to assess the impact of pre-existing immunity to DENV on ZIKV pathogenesis during pregnancy. We did not observe any difference in ZIKV replication in plasma between macaques that were immune to DENV and those that were not. However, there was more ZIKV vRNA detected in the placenta of macaques immune to DENV, suggesting DENV immunity could enhance ZIKV infection of the placenta. As vaccines to both DENV and ZIKV are developed, it remains critical to understand the risks of DENV immunity for pregnant women exposed to ZIKV.
- Published
- 2021