Abstract
Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.
Highlights
Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues
Reduced CD8 T cell response to ZIKVBR infection correlates with virus detection at later time points post-infection
To determine whether an epidemic ZIKV isolate differs in its capacity to induce CD8 T cell responses, we compared the response induced by infection with ZIKVCDN to the response induced by infection with HS-2015-BA-01, a Brazilian isolate from the 2015 South and Central American outbreak
Summary
Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. In STAT2 KO mice, mortality correlated with induction of IFN-α and IFN-β mRNA, with the highest levels observed following infection with the Ugandan isolate MR766 (African lineage)[19] These studies were undertaken in immunocompromised hosts, which limits their usefulness in interrogating immune responses to infection, they suggest that contemporary ZIKV isolates induce a less inflammatory and less lethal infection than historical ZIKV isolates. Our data demonstrated that an early Asian lineage ZIKV isolate (PLCal_ZV, accession number KF993678; referred to as ZIKVCDN) establishes an active, albeit rapidly cleared, infection in C57BL/6 wild type (WT) mice[22] This leads to a robust and prototypical antiviral innate immune response, including dendritic cell (DC) and natural killer cell activation[22]. Since the mice are immunocompetent and do not succumb to infection, this model allows us to query the impact of epidemic ZIKV isolates on antiviral cytotoxic T cell responses
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