A Rat Model of Prenatal Zika Virus Infection and Associated Long-Term Outcomes.

Morgan L Sherer,Elise A Lemanski,Mark S Parcells,Rita T Patel,Shannon R Wheeler,Jaclyn M Schwarz

doi:10.3390/v13112298

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus that became widely recognized due to the epidemic in Brazil in 2015. Since then, there has been nearly a 20-fold increase in the incidence of microcephaly and birth defects seen among women giving birth in Brazil, leading the Centers for Disease Control and Prevention (CDC) to officially declare a causal link between prenatal ZIKV infection and the serious brain abnormalities seen in affected infants. Here, we used a unique rat model of prenatal ZIKV infection to study three possible long-term outcomes of congenital ZIKV infection: (1) behavior, (2) cell proliferation, survival, and differentiation in the brain, and (3) immune responses later in life. Adult offspring that were prenatally infected with ZIKV exhibited motor deficits in a sex-specific manner, and failed to mount a normal interferon response to a viral immune challenge later in life. Despite undetectable levels of ZIKV in the brain and serum in these offspring at P2, P24, or P60, these results suggest that prenatal exposure to ZIKV results in lasting consequences that could significantly impact the health of the offspring. To help individuals already exposed to ZIKV, as well as be prepared for future outbreaks, we need to understand the full spectrum of neurological and immunological consequences that could arise following prenatal ZIKV infection.

Highlights

Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family and belongs to the same genus, Flavivirus, as Dengue, West Nile, and Yellow Fever viruses [1].ZIKV was first discovered in 1947 from a sentinel rhesus macaque in Uganda and the virus remained in relative obscurity for decades until 2007, when it caused its first noteworthy epidemic on Yap island in Micronesia, and in 2013 when it reached New Caledonia, French Polynesia, and most extensively, Brazil in 2015 [2,3]
On embryonic day 18 (E18), pregnant females were transported to a Biosafety Level 2 (BSL2) animal isolation facility where they were individually housed for the remainder of their pregnancy
The current study explored long-term behavioral and molecular alterations following gestational ZIKV exposure in a rat model of prenatal ZIKV infection

Summary

Introduction

Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family and belongs to the same genus, Flavivirus, as Dengue, West Nile, and Yellow Fever viruses [1].ZIKV was first discovered in 1947 from a sentinel rhesus macaque in Uganda and the virus remained in relative obscurity for decades until 2007, when it caused its first noteworthy epidemic on Yap island in Micronesia, and in 2013 when it reached New Caledonia, French Polynesia, and most extensively, Brazil in 2015 [2,3]. Zika virus (ZIKV) is a positive-stranded RNA virus within the Flaviviridae family and belongs to the same genus, Flavivirus, as Dengue, West Nile, and Yellow Fever viruses [1]. ZIKV has been shown to be transmitted through other routes including sexual transmission, transfusion of blood products, breast milk feeding, as well as vertical transmission from mother to fetus [4]. Clinical symptoms of ZIKV infection in adults are similar to other flavivirus infections (such as dengue fever) and include fever, headache, joint pain, muscle pain, and maculopapular rash. More severe clinical outcomes of ZIKV infection have been reported such as the neurological disorder Guillain–Barré syndrome; these consequences are comparatively very rare [1]

Methods

Results

Conclusion