[18F]DPA 714 PET Imaging Reveals Global Neuroinflammation in Zika Virus Infected Mice
Journal Article - Open Access
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD FORT DETRICK United States
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The association of Zika virus ZIKV infection and the development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography PET imaging using 18FDPA-714, a translocator protein TSPO 18 kDa radioligand, to detect and quantify neuroinflammation in ZIKV-infected mice. We assessed ZIKV-induced pathogenesis in wild-type C57BL6 mice treated with an antibody to disrupt type I interferon IFN signaling. 18FDPA-714 PET imaging was performed on days 3, 6, and 10 post-infection PI, and tissues were subsequently processed for histological evaluation, quantification of microgliosis, and detection of viral RNA by in situ hybridization ISH. In susceptible ZIKV-infected mice, viral titers in the brain increased from day 3to day 10 PI. Over this span, these mice showed a 2- to 6-fold increase in global brain neuroinflammation using 18FDPA-714 PET imaging despite limited, regional detection of viral RNA. No measurable increase in ionized calcium binding adaptor molecule 1Iba-1 expression was noted at day 3 PI however, there was a modest increase at day 6PI and a significant 4-fold increase in Iba-1 expression at day 10 PI in the susceptible ZIKV-infected group relative to controls. The results of the current study demonstrate that global neuroinflammation plays a significant role in the progression of ZIKV infection and that 18FDPA-714 PET imaging is a sensitive tool relative to histology for the detection of neuroinflammation.18FDPA-714 PET imaging and potentially other PET probes may be useful in dynamically characterizing the pathology associated with neurotropic viruses and the evaluation of therapeutics being developed for treatment of infectious diseases.
- Medicine and Medical Research