Abstract
Abstract Zika virus (ZIKV) is a mosquito-borne pathogen that recently gained international attention following a major epidemic in South and Central America. The most striking aspect of this epidemic was the novel association of ZIKV infection with neurological symptoms, such as fetal microcephaly. In addition, ZIKV may persist in humans for 15- and 42-days post-symptom onset in serum and semen, respectively. Therefore, our objective was to investigate whether recent ZIKV isolates have an enhanced capacity to evade host immunity. To address this objective, we have established an immunocompetent mouse model of ZIKV infection, in which infection with pre-epidemic, early Asian lineage ZIKV isolate (ZIKV-CDN) induces robust type I interferon (IFN) production and prototypical Th1 CD4 and effector CD8 T cell responses. We are now comparing this baseline to the immune response induced by a ZIKV isolate from the Brazilian epidemic (ZIKV-BR). Our data demonstrate a dramatic suppression of type I IFN production during ZIKV-BR infection, which correlates with a severe reduction in the CD8 T cell response. Co-infection reduces the magnitude of the CD8 T cell response when compared to infection with ZIKV-CDN alone, suggesting ZIKV-BR actively interferes with the host immune response. As a result, ZIKV-BR establishes a sustained infection, with high viral loads detected as late as 7 days post-infection. Future studies will aim to determine why less type I interferons are produced, and the impact of ZIKV-BR infection on the CD4 T cell response. Together, our data suggest that contemporary strains of ZIKV have evolved novel ways of countering host immunity, which could explain, at least in part, the increased pathogenicity observed in recent outbreaks.
Published Version
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