Host Immune Response to ZIKV in an Immunocompetent Embryonic Mouse Model of Intravaginal Infection
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Authors
Khaiboullina, Svetlana F.
Lopes, Priscila
de Carvalho, Toniana G.
Real, Ana Luiza C. V.
Souza, Danielle G.
Costa, Vivian V.
Teixeira, Mauro M.
Bloise, Enrrico
Verma, Subhash C.
Ribeiro, Fabiola M.
Issue Date
2019
Type
Article
Language
Keywords
ZIKV , FVB/NJ mice , intravaginal infection , CCL2 , CXCL1 and CXCL10
Alternative Title
Abstract
Zika virus (ZIKV) only induces mild symptoms in adults
however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of the host immune response to ZIKV becomes challenging in these animals. Thus, the main goal of this study was to develop an immunocompetent mouse model to study the ZIKV spread and teratogeny. FVB/NJ immune competent dams were infected intravaginally with ZIKV during the early stage of pregnancy. We found that the placentae of most fetuses were positive for ZIKV, while the virus was detected in the brain of only about 42% of the embryos. To investigate the host immune response, we measured the expression of several inflammatory factors. Embryos from ZIKV-infected dams had an increased level of inflammatory factors, as compared to Mock. Next, we compared the gene expression levels in embryos from ZIKV-infected dams that were either negative or positive for ZIKV in the brain. The mRNA levels of viral response genes and cytokines were increased in both ZIKV-positive and negative brains. Interestingly, the levels of chemokines associated with microcephaly in humans, including CCL2 and CXCL10, specifically increased in embryos harboring ZIKV in the embryo brains.
however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of the host immune response to ZIKV becomes challenging in these animals. Thus, the main goal of this study was to develop an immunocompetent mouse model to study the ZIKV spread and teratogeny. FVB/NJ immune competent dams were infected intravaginally with ZIKV during the early stage of pregnancy. We found that the placentae of most fetuses were positive for ZIKV, while the virus was detected in the brain of only about 42% of the embryos. To investigate the host immune response, we measured the expression of several inflammatory factors. Embryos from ZIKV-infected dams had an increased level of inflammatory factors, as compared to Mock. Next, we compared the gene expression levels in embryos from ZIKV-infected dams that were either negative or positive for ZIKV in the brain. The mRNA levels of viral response genes and cytokines were increased in both ZIKV-positive and negative brains. Interestingly, the levels of chemokines associated with microcephaly in humans, including CCL2 and CXCL10, specifically increased in embryos harboring ZIKV in the embryo brains.
Description
Citation
Khaiboullina, S. F., Lopes, P., de Carvalho, T. G., Real, A. L. C. V., Souza, D. G., Costa, V. V., … Ribeiro, F. M. (2019). Host Immune Response to ZIKV in an Immunocompetent Embryonic Mouse Model of Intravaginal Infection. Viruses, 11(6), 558. doi:10.3390/v11060558
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License
Creative Commons Attribution 4.0 International
Journal
Volume
Issue
PubMed ID
ISSN
1999-4915