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Vascular Localization of Zika Virus Following in vivo Infection
Author(s) -
Brown Isola A.M.,
DeLalio Leon J.,
Liu Shufeng,
Isakson Brant E.,
Wang Tony T.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.902.8
Subject(s) - zika virus , virology , in vivo , flavivirus , biology , immunohistochemistry , virus , microcephaly , antibody , endothelium , immunology , medicine , pathology , genetics , microbiology and biotechnology , endocrinology
Zika virus (ZIKV) is an emerging blood‐borne pathogen that produces flu‐like symptoms in infected individuals and is responsible for microcephaly and other neonatal birth defects. Despite this growing public health concern, the molecular mechanisms involved in ZIKV infection are still poorly understand. We have recently shown that African and South American derived ZIKV strains infect human endothelial cells in culture (Liu et al., Circ Res , 2016). Still, the role of the vasculature and endothelium during in vivo infection are not known. We investigated a role for the vasculature in ZIKV infection and hypothesize that ZIKV expression in infected animals will localize to vascular beds. We established ZIKV infection using an in vivo animal model of infection in 4‐week old C57Bl/6 mice. Mice received 6.4×10 6 plaque forming units (PFUs) of either the PRVABC59 or DAK strains of ZIKV, isolated in Puerto Rico and Senegal respectively. Mice were sacrificed at 5 days post‐infection and we used immunohistochemistry to detect ZIKV expression in various vascular beds including brain, liver, aorta and mesenteric. ZIKV was labeled using a novel murine monoclonal antibody D1‐4G2‐4‐15 against the viral coat protein E‐protein. At 5 days post‐infection (dpi), mice treated with the DAK strain have decreased body weight compared to Day 0, while mice treated with the PRV are resistant to this weight loss. At 5 dpi, both groups of mice have increased brain ZIKV viral loads. However, the viral load in DAK mice was four‐fold that of PRV‐treated mice. Mice treated with DAK show increased morbidity with 0% survival at 7 dpi while the PRV strain is non‐lethal up to 15 dpi. At 5 dpi, the ZIKV viral coat protein E protein was detectable in arteries and veins of the cerebral circulation from brains of mice treated with either ZIKV strain and co‐localized with the endothelial marker claudin‐5. Interestingly, cerebral capillaries were found to have the DAK ZIKA, whereas the PRV did not. The co‐localization of ZIKV with endothelial markers suggests a role in the pathology of in vivo ZIKV infection. These findings improve our understanding of the pathology of ZIKV infection and hint at potential strain variation that may be mediated by endothelium. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .