scholarly journals Pregnancy alters innate immune responses to Zika virus infection in the genital tract

2019 ◽  
Author(s):  
Kelsey E. Lesteberg ◽  
Dana S. Fader ◽  
J. David Beckham
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Zika Virus ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Innate Immune Responses ◽  
Zikv Infection ◽  
Zika Virus Infection ◽  
Pregnant Mice

AbstractRecent outbreaks of Zika virus (ZIKV) have been associated with birth defects, including microcephaly and neurological impairment. However, the mechanisms which confer increased susceptibility to ZIKV during pregnancy remain unclear. We hypothesized that poor outcomes from ZIKV infection during pregnancy are due in part to pregnancy-induced alteration of innate immune cell frequencies and cytokine expression. To examine the impact of pregnancy on innate immune responses, we inoculated pregnant and non-pregnant female C57BL/6 mice with 5×105 FFU of ZIKV intravaginally. Innate immune cell frequencies and cytokine expression were measured by flow cytometry at day 3 post infection. Compared to non-pregnant mice, pregnant mice exhibited higher frequencies of uterine macrophages (CD68+) and tolerogenic dendritic cells (CD11c+ CD103+ and CD11c+ CD11b+). Additionally, ZIKV-infected pregnant mice had lower frequencies of CD45+ IL-12+ and CD11b+ IL-12+ cells in the uterus and spleen. These data show that pregnancy results in an altered innate immune response to ZIKV infection in the genital tract of mice and that pregnancy-associated immune modulation may play an important role in the severity of acute ZIKV infection.ImportancePregnant females longer duration that viremia following infection with Zika virus but the mechanism of this is not established. Innate immune cellular responses are important for controlling virus infection and are important for development and maintenance of pregnancy. Thus, the acute immune response to Zika virus during pregnancy may be altered so that the pregnancy can be maintained. To examine this interaction, we utilized a mouse model of Zika virus infection during pregnancy using intravaginal inoculation. We found that following Zika virus infection, pregnant mice exhibited increased expression of tolerant or non-inflammatory dendritic cells. Additionally, we found that pregnant mice have significantly depressed ability to secrete the cytokine IL-12 from innate immune cells in the uterus and the spleen while maintaining MHCII expression. These findings show that pregnancy-induced changes in the innate immune cells are biased towards tolerance and can result in decreased antigen-dependent stimulation of immune responses.

scholarly journals Zika virus alters centrosome organization to suppress the innate immune response

2020 ◽  
Author(s):  
Andrew Kodani ◽  
Kristeene A. Knopp ◽  
Elizabeth Di Lullo ◽  
Hanna Retallack ◽  
Arnold R. Kriegstein ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Zika Virus ◽  
Nonstructural Protein ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Zikv Infection ◽  
Centrosomal Proteins ◽  
Nonstructural Protein Ns3

AbstractZika virus (ZIKV) is a flavivirus transmitted via mosquitoes and sex to cause congenital neurodevelopmental defects, including microcephaly. Inherited forms of microcephaly (MCPH) are associated with disrupted centrosome organization. Similarly, we found that ZIKV infection disrupted centrosome organization. ZIKV infection disrupted the organization of centrosomal proteins including CEP63, a MCPH-associated protein. The ZIKV nonstructural protein NS3 bound CEP63, and expression of NS3 was sufficient to alter centrosome architecture and CEP63 localization. Loss of CEP63 suppressed ZIKV-induced centrosome disorganization, indicating that ZIKV requires CEP63 to disrupt centrosome organization. ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. Therefore, we propose that ZIKV NS3 binds CEP63 to increase centrosomal DTX4 localization and destabilization of TBK1, thereby tempering the innate immune response. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly.

scholarly journals Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Yiska Weisblum ◽  
Esther Oiknine-Djian ◽  
Olesya M. Vorontsov ◽  
Ronit Haimov-Kochman ◽  
Zichria Zakay-Rones ◽  
...  
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Innate Immune ◽  
Tissue Response ◽  
Therapeutic Interventions ◽  
Innate Immune Responses ◽  
Zikv Infection ◽  
Viral Spread ◽  
Tissue Responses ◽  
Maternal Fetal Interface

ABSTRACT Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. IMPORTANCE In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission.

scholarly journals Transfer of convalescent serum to pregnant mice prevents Zika virus infection and microcephaly in offspring

Cell Research ◽  
2016 ◽  
Vol 27 (1) ◽  
pp. 158-160 ◽  
Author(s):  
Shuo Wang ◽  
Shuai Hong ◽  
Yong-Qiang Deng ◽  
Qing Ye ◽  
Ling-Zhai Zhao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Zika Virus ◽  
Zika Virus Infection ◽  
Pregnant Mice

scholarly journals Aedes aegypti Saliva Enhances Dengue Virus Infection of Human Keratinocytes by Suppressing Innate Immune Responses

2012 ◽  
Vol 132 (8) ◽  
pp. 2103-2105 ◽  
Author(s):  
Pornapat Surasombatpattana ◽  
Sirilaksana Patramool ◽  
Natthanej Luplertlop ◽  
Hans Yssel ◽  
Dorothée Missé
Keyword(s):  
Virus Infection ◽  
Aedes Aegypti ◽  
Immune Responses ◽  
Dengue Virus ◽  
Human Keratinocytes ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Dengue Virus Infection
Sign in / Sign up

Export Citation Format

Share Document