About: Life-long persistence of infectious Zika virus: inflammation and behavioral sequela

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About: Life-long persistence of infectious Zika virus: inflammation and behavioral sequela Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Life-long persistence of infectious Zika virus: inflammation and behavioral sequela
Creator	Verthelyi, Daniela Manangeeswaran, Mohanraj Ireland, Derek Lee, Ha Clark, Sarah Engel, Kaliroi Kelly-Baker, Logan Laniyan, Adelle Lewkowicz, Aaron Mcwilliams, Ian Sykes, Jacob Tonelli, Leonardo
Source	BioRxiv
abstract	The recent spread of Zika virus (ZIKV) and its association with congenital defects and neurological disorders has created an urgent need to understand the pathogenesis of ZIKV and identify therapeutic strategies that will prevent or eliminate them. The neurodevelopmental defects associated with ZikV infections early in pregnancy are well documented, however the potential defects associated with infections in late pregnancy and perinatal period are less well characterized. Further, the long-term sequelae of these infections are not fully understood. Immunocompetent C57BL/6 mice infected at one day old (P1), which neurodevelopmentally model late pregnancy in humans, develop a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subside after a week, and most animals survive. Despite apparent recovery, MRI of convalescent mice shows reduced cerebellar volume that correlates with altered coordination and motor function as well as hyperactivity and impulsivity. Persistent mRNA levels of pro-inflammatory genes including Cd80, Il-1α, and Ifn-γ together with Cd3, Cd8 and perforin (PrfA), suggested the persistence of a low-grade inflammatory process. Further, the brain parenchyma of convalescent mice harbor multiple small 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. Detection of negative-sense strand viral RNA and replication of virus derived from these convalescent mice by blinded passage in Vero cells confirmed that low levels of live ZikV persist in CNS of convalescent mice life-long. Our studies establish that Zika can establish reservoirs in CNS and suggest that anti-viral treatment that clears virus from the CNS as well as long-term neurological and behavioral monitoring may be needed for patients known to be exposed to ZikV at an early age. Author’s summary The congenital brain malformations associated with ZikV infections early in pregnancy are well documented, however whether apparently asymptomatic perinatal exposure could lead to long term sequelae is not fully understood. Using a non-lethal neonatal mouse model, we examine host-pathogen interactions, anatomical changes and behavioral patterns by following survivors of the acute infection for over 1 year. We discover that infectious Zika virus has the potential to remain in the CNS for life, lodged within small foci surrounded by gliosis and infiltrating immune cells that may act to limit the viral spread, but also interfere with healing and contribute to life-long neuropathic and behavioral sequelae. These results suggest that anti-viral treatment and long-term neurological and behavioral monitoring may be indicated for patients known to have been exposed to Zika virus, regardless of neurodevelopmental disease severity.
has issue date	2020-06-11(xsd:dateTime)
bibo:doi	10.1101/2020.06.11.145854
has license	biorxiv
sha1sum (hex)	80f690f873a4dfd0dc5310780e819f8efb4a4f63
schema:url	https://doi.org/10.1101/2020.06.11.145854
resource representing a document's title	Life-long persistence of infectious Zika virus: inflammation and behavioral sequela
schema:publication	bioRxiv
resource representing a document's body	covid:80f690f873a4dfd0dc5310780e819f8efb4a4f63#body_text
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