Zika Virus Localizes to Vascular Endothelial and Smooth Muscle Cells following In Vivo Infection

Abstract

Zika virus (ZIKV) is a public health concern due to its classification as a bloodborne pathogen. However, the pathology of ZIKV— i.e. its mechanisms of infection – is not been fully understood. We and other researchers have recently discovered that multiple ZIKV strains readily infect primary human endothelial cells (ECs). However, the cellular targets of the virus during in vivo whole animal infection are not known. We investigated the role of the intact vasculature in ZIKV infection and hypothesized that ZIKV will be localized to ECs following in vivo infection.7‐week old male C57Bl/6 mice were treated using an established in vivo animal model of ZIKV infection. Mice received ZIKV strains isolated from either an African (DAK) or South American (PRV) viral outbreak. Mice were sacrificed 7 days post‐infection and we used immunohistochemistry to detect ZIKV expression in collected vessels including the aorta, mesenteric arteries and veins, the renal artery, and the cremasteric and retinal vasculatures. ZIKV virus was labeled anti‐4G2, which marks a viral coat protein of ZIKV, and ECs were labeled with anti‐CD31.Mice treated with the DAK strain showed positive localization in the smooth muscle cells (SMCs) of the cremaster preparation, ECs of mesenteric vessels, and SMCs and ECs of the renal artery. Those treated with the PRV strain also showed localization in the ECs of the cremaster and mesenteric vasculatures, and both the SMCs and ECs of the renal artery. There was no positive ZIKV localization found in the retina.Positive localization of ZIKV in the vascular beds of the cremaster, mesenteric vessels, and renal artery suggests a role for the ECs and SMCs of the vasculature in the pathology of ZIKV infection. Future work will investigate key cellular targets that may be in involved in regulating in vivo ZIKV infection, such as the AXL tyrosine kinase receptor AXL which is required for ZIKV infection in vitro. These and future studies will improve our understanding of the pathology of ZIKV infection.Support or Funding InformationFord Foundation Postdoctoral Grant (IAMB), HL 088554 R01 (BEI)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.