key: cord-0049622-t31jvurj
authors: Bai, Chongzhi; Li, Shihua; Song, Shen; Wang, Qihui; Cho, HeeCheol; Gao, George Fu; Nie, Yu; Han, Pengcheng
title: Zika virus induces myocardial immune response and myocarditis in mice
date: 2020-09-06
journal: J Mol Cell Cardiol
DOI: 10.1016/j.yjmcc.2020.08.014
sha: 96aa124328bbf7a4035a9bbeb0781fd88b1e0328
doc_id: 49622
cord_uid: t31jvurj

nan

Recently, ZIKV was detected in heart tissue (3), but the pathophysiological processes of ZIKV causing cardiovascular implications are still unclear (4). Here, we established a mouse model of ZIKV pathogenesis and found that ZIKV can directly infect cardiomyocytes, causing myocardial inflammation, myocarditis, and heart function impairment. Our findings provide evidence to understand the heart involvement in ZIKV-infected patients, which may be essential for protecting them from life-threatening complications.

ZIKV is transmitted through mosquito bites, sex, blood transfusions, and from consistent with previous studies (6, 7) .

To examine whether direct infection occurred in the mouse myocardium, ZIKV was detected by immunofluorescence using the monoclonal antibody Z6 (7, 8) . We found that Z6 was localized in cardiomyocytes (α-actinin + ) of ZIKV-IP KO mice at 10 DPI (Fig. 1a) and Z6 was not observed in the heart of ZIKV-IP wild type (WT) mice at 10 DPI (Fig. S1a) . Terminal dexynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays revealed that cardiomyocyte apoptosis was dramatically increased in ZIKV-infected mice at 10 DPI (Fig. 1b) . Masson's staining revealed that myocardial fibrosis was significantly increased at 10 DPI in ZIKV-IP KO mice at 10 DPI (Fig. 1c, d) but myocardial fibrosis was not observed in ZIKV-IP WT mice at 10 DPI (Fig. S1b) . Echocardiography demonstrated the deterioration of fractional shortening and the ejection fraction at 10 DPI and 15 DPI compared to uninfected mice (Fig. 1e) . Electro-Chemiluminescence-Assays revealed that the level of CK-MB (creatine kinase-muscle/brain) and cTnT (troponin T) were dramatically elevated in serum at 5, 10, and 15 DPI (Fig. 1f) , indicating that cardiac injury occurred. Our results indicated that ZIKV can directly infect the myocardium and lead to cardiomyocyte death, myocardial injury, cardiac fibrosis, and heart dysfunction in Immunohistochemistry displays that F4/80 + macrophages and CD3 + leucocytes are increased significantly in myocardium relative to uninfected mice at 10 DPI. n = 5 in each group.

i Flow cytometry indicates that both CD3 + CD4 + leucocytes and NK1.1 + cells are evaluated in peripheral blood at 5, 10 and 15 DPI in ZIKV-infected mice, respectively. n = 5 in each group.

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