BACKGROUND
Infection with
Zika virus (
ZIKV ) manifests in a broad spectrum of
disease ranging from mild illness to severe neurological
complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic
biomarkers that correlate with acute
ZIKV infection .
METHODS We characterized the levels of circulating
cytokines ,
chemokines , and
growth factors in 54 infected
patients of both genders at five different
time points after symptom onset using
microbeads multiplex
immunoassay ; comparison to 100 age-matched controls was performed for
statistical analysis and
data mining . FINDINGS
ZIKV -infected
patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern,
IL-1Ra and
IL-4 are also induced during the acute
infection . Interestingly, the inflammatory
cytokines IL-1 β,
IL-13 ,
IL-17 , TNF-α, and IFN-γ;
chemokines CXCL8, CCL2, CCL5; and the
growth factor G-CSF , displayed a bimodal distribution accompanying
viremia . While this is the first manuscript to
document bimodal distributions of
viremia in
ZIKV infection , this has been documented in other
viral infections , with a primary
viremia peak during mild systemic
disease and a
secondary peak associated with distribution of the
virus to organs and
tissues . MAIN CONCLUSIONS
Biomarker network
analysis demonstrated distinct dynamics in concurrence with the bimodal
viremia profiles at different
time points during
ZIKV infection . Such a robust
cytokine and
chemokine response has been associated with
blood-brain barrier permeability and neuroinvasiveness in other flaviviral
infections . High-dimensional
data analysis further identified CXCL10, a
chemokine involved in foetal
neuron apoptosis and
Guillain-Barré syndrome , as the most promising
biomarker of acute
ZIKV infection for potential clinical application.