In a small number of cases ZIKV infections have been linked to more serious neurological disease including: Guillain Barre Syndrome, acute myelitis, encephalitis and polyneuropathies, as well as chorioretinitis. Zika infections are asymptomatic in most adults, but approximately 20% of patients develop fever, rash, conjunctivitis, muscle and joint pain. Although transmission of ZIKV has since declined, WHO now considers Zika endemic to many areas of the world and infection clusters continue to be reported in regions of Cuba, India and Southeast Asia, where there are large populations of women of childbearing age who are susceptible to the virus. Zika virus (ZIKV) is an arbovirus from the Flaviviridae family that caused a world-wide public health emergency between 20 as over 750,000 cases were reported in 84 countries, including over 40,000 in the US. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: No authors have competing interests. from the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. This study was supported in part by Senior Postgraduate Research Fellowship Awards to A.P.L., H-N.L., I.M.W., K.E., and J.S. and by a Center of Excellence in Regulatory Science and Innovation (CERSI) grant to University of Maryland from the US Food & Drug Administration (Grant: U01FD005946) for L.H.T. The work is made available under the Creative Commons CC0 public domain dedication.ĭata Availability: All relevant data are within the manuscript and its supporting information files.įunding: This work was supported in part by the FDA’s Office of Counter-terrorism and Emerging Threat to D.V.
#Side effect of zika virus free
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: JAccepted: OctoPublished: December 10, 2020 Lazear, University of North Carolina at Chapel Hill School of Medicine, UNITED STATES
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(2020) Long-term persistence of infectious Zika virus: Inflammation and behavioral sequela in mice. This raises concern regarding possible long-term effects in asymptomatic children exposed to the virus and suggests that long-term neurological and behavioral monitoring as well as anti-viral treatment to clear virus from the CNS may be useful in patients exposed to ZIKV at an early age.Ĭitation: Ireland DDC, Manangeeswaran M, Lewkowicz AP, Engel K, Clark SM, Laniyan A, et al. Although the infection appears to persist in defined reservoirs within CNS, the resulting inflammation could increase the risk of neurodegenerative disorders.
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Detection of negative-sense strand viral RNA and isolation of infectious virus derived from these convalescent mice by blinded passage in Vero cells confirmed long-term persistence of replicating ZIKV in CNS of convalescent mice.
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Surprisingly, the brain parenchyma of convalescent mice harbor multiple small discrete foci with viral antigen, active apoptotic processes in neurons, and cellular infiltrates, surrounded by activated astrocytes and microglia as late as 1-year post-infection. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin ( PrfA), suggested persistence of low-grade inflammation. Despite apparent recovery, MRI of convalescent mice show reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. The animals developed a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10–15 days post-infection (dpi) but symptoms subsided after a week, and most animals survived.
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To model these, we challenged 1 day old (P1) immunocompetent C57BL/6 mice with ZIKV. The neurodevelopmental defects associated with ZIKV infections early in pregnancy are well documented, however the potential defects and long-term consequences associated with milder infections in late pregnancy and perinatal period are less well understood.