scholarly journals A ‘Furry-Tale’ of Zika Virus Infection: What Have We Learned from Animal Models?

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 29 ◽  
Author(s):  
Loulieta Nazerai ◽  
Jan Pravsgaard Christensen ◽  
Allan Randrup Thomsen
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Zika Virus ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Zikv Infection ◽  
Infected People ◽  
Collective Effort ◽  
Transplacental Infection

The worldwide attention that the Zika virus (ZIKV) attracted, following its declaration as a Public Health Emergency of International concern by WHO in 2016, has led to a large collective effort by the international scientific community to understand its biology. Despite the mild symptoms caused by ZIKV in most infected people, the virus displays a number of worrying features, such as its ability to cause transplacental infection, fetal abnormalities and vector independent transmission through body fluids. In addition, the virus has been associated with the induction of Guillain-Barre syndrome in a number of infected individuals. With travelling, the virus has spread outside the original ZIKV endemic areas making it imperative to find ways to control it. Thus far, the large number of animal models developed to study ZIKV pathogenesis have proven to be valuable tools in understanding how the virus replicates and manifests itself in the host, its tissue tropism and the type of immune responses it induces. Still, vital questions, such as the molecular mechanisms of ZIKV persistence and the long-term consequences of ZIKV infection in the developing brain, remain unanswered. Here, we reviewed and discussed the major and most recent findings coming from animal studies and their implications for a ZIKV vaccine design.

scholarly journals Molecular mechanisms of Zika virus teratogenesis from animal studies: a systematic review protocol

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Gabriela Elis Wachholz ◽  
Julia do Amaral Gomes ◽  
Juliano André Boquett ◽  
Fernanda Sales Luiz Vianna ◽  
Lavínia Schuler-Faccini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Zika Virus ◽  
Methodological Quality ◽  
Molecular Mechanisms ◽  
Grey Literature ◽  
Standard Form ◽  
Teratogenic Effect ◽  
Control Group

Abstract Background Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models. Methods This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE’s Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular). Discussion With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability. Systematic review registration PROSPERO CRD42019157316

scholarly journals Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair

2021 ◽  
Vol 22 (3) ◽  
pp. 1201
Author(s):  
Hsuan Peng ◽  
Kazuhiro Shindo ◽  
Renée R. Donahue ◽  
Ahmed Abdel-Latif
Keyword(s):  
Stem Cell ◽  
Immune Responses ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Cell Delivery ◽  
Cardiac Cell Therapy ◽  
Stem Cell Treatment

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

scholarly journals Improved Immune Responses against Zika Virus after Sequential Dengue and Zika Virus Infection in Human

2018 ◽  
Author(s):  
Felix G. Delgado ◽  
Karina I. Torres ◽  
Jaime E. Castellanos ◽  
Consuelo Romero-Sánchez ◽  
Etienne Simon-Lorière ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Denv Infection ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses ◽  
B Cell Responses

The high level of dengue virus (DENV) seroprevalence in areas where Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infection. To determine the role of DENV pre-immunity in ZIKV infection, we analysed the T and B cell responses against ZIKV in donors with or without previous DENV infection. Using PBMCs from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the non-structural proteins NS1, NS3 and NS5. Analyses of the T and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors, in comparison with DENV-naïve donors. Strikingly, the potential for antibody mediated enhancement of ZIKV infection was reduced in donors with sequential DENV and ZIKV infection in comparison with donors with DENV infection only. Altogether, these data suggest that individuals with DENV immunity present improved immune responses against ZIKV.

scholarly journals Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Scientific Community ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Rapid Testing ◽  
Zikv Infection ◽  
Male Reproductive Tract

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

scholarly journals Animal Models of Zika Virus Infection during Pregnancy

Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 598 ◽  
Author(s):  
Elizabeth Caine ◽  
Brett Jagger ◽  
Michael Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Congenital Abnormalities ◽  
Tissue Tropism ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Sexually Transmitted

Zika virus (ZIKV) emerged suddenly in the Americas in 2015 and was associated with a widespread outbreak of microcephaly and other severe congenital abnormalities in infants born to mothers infected during pregnancy. Vertical transmission of ZIKV in humans was confirmed when viral RNA was detected in fetal and placental tissues, and this outcome has been recapitulated experimentally in animals. Unlike other flaviviruses, ZIKV is both arthropod- and sexually-transmitted, and has a broad tissue tropism in humans, including multiple tissues of the reproductive tract. The threats posed by ZIKV have prompted the development of multiple in vivo models to better understand the pathogenesis of ZIKV, particularly during pregnancy. Here, we review the progress on animal models of ZIKV infection during pregnancy. These studies have generated a foundation of insights into the biology of ZIKV, and provide a means for evaluating vaccines and therapeutics.

scholarly journals Simian Immunodeficiency Virus Infection of Rhesus Macaques Results in Delayed Zika Virus Clearance

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Carol L. Vinton ◽  
Samuel J. Magaziner ◽  
Kimberly A. Dowd ◽  
Shelly J. Robertson ◽  
Emerito Amaro-Carambot ◽  
...  
Keyword(s):  
Immune Responses ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Type I Interferons ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Zikv Infection ◽  
Adaptive Immune ◽  
Immunodeficiency Virus

ABSTRACT Flaviviruses are controlled by adaptive immune responses but are exquisitely sensitive to interferon-stimulated genes (ISGs). How coinfections, particularly simian immunodeficiency viruses (SIVs), that induce robust ISG signatures influence flavivirus clearance and pathogenesis is unclear. Here, we studied how Zika virus (ZIKV) infection is modulated in SIV-infected nonhuman primates. We measured ZIKV replication, cellular ZIKV RNA levels, and immune responses in non-SIV-infected and SIV-infected rhesus macaques (RMs), which we infected with ZIKV. Coinfected animals had a 1- to 2-day delay in peak ZIKV viremia, which was 30% of that in non-SIV-infected animals. However, ZIKV viremia was significantly prolonged in SIV-positive (SIV+) RMs. ISG levels at the time of ZIKV infection were predictive for lower ZIKV viremia in the SIV+ RMs, while prolonged ZIKV viremia was associated with muted and delayed adaptive responses in SIV+ RMs. IMPORTANCE Immunocompromised individuals often become symptomatic with infections which are normally fairly asymptomatic in healthy individuals. The particular mechanisms that underlie susceptibility to coinfections in human immunodeficiency virus (HIV)-infected individuals are multifaceted. ZIKV and other flaviviruses are sensitive to neutralizing antibodies, whose production can be limited in HIV-infected individuals but are also sensitive to type I interferons, which are expressed at high levels in HIV-infected individuals. Data in this study highlight how individual components of the innate and adaptive immune responses which become perturbed in HIV-infected individuals influence ZIKV infection.

scholarly journals Immunogenicity and Efficacy of Zika Virus Envelope Domain III in DNA, Protein, and ChAdOx1 Adenoviral-Vectored Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 307 ◽  
Author(s):  
César López-Camacho ◽  
Giuditta De Lorenzo ◽  
Jose Luis Slon-Campos ◽  
Stuart Dowall ◽  
Peter Abbink ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Protein Domain ◽  
Virus Envelope ◽  
Zikv Infection ◽  
Domain Iii ◽  
Open Question

The flavivirus envelope protein domain III (EDIII) was an effective immunogen against dengue virus (DENV) and other related flaviviruses. Whether this can be applied to the Zika virus (ZIKV) vaccinology remains an open question. Here, we tested the efficacy of ZIKV-EDIII against ZIKV infection, using several vaccine platforms that present the antigen in various ways. We provide data demonstrating that mice vaccinated with a ZIKV-EDIII as DNA or protein-based vaccines failed to raise fully neutralizing antibodies and did not control viremia, following a ZIKV challenge, despite eliciting robust antibody responses. Furthermore, we showed that ZIKV-EDIII encoded in replication-deficient Chimpanzee adenovirus (ChAdOx1-EDIII) elicited anti-ZIKV envelope antibodies in vaccinated mice but also provided limited protection against ZIKV in two physiologically different mouse challenge models. Taken together, our data indicate that contrary to what was shown for other flaviviruses like the dengue virus, which has close similarities with ZIKV-EDIII, this antigen might not be a suitable vaccine candidate for the correct induction of protective immune responses against ZIKV.

ANTI-EPILEPTIC DRUGS AND BRAIN AND BEHAVIOURAL DEVELOPMENT IN ANIMAL MODELS AND HUMANS

2010 ◽  
Vol 21 (4) ◽  
pp. 283-306
Author(s):  
NAGHME ADAB ◽  
MICHAEL F O'DONOGHUE
Keyword(s):  
Animal Models ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Developmental Problems ◽  
Gestational Exposure ◽  
Behavioural Effects ◽  
Confounding Variables ◽  
Long Time ◽  
Behavioural Repertoire ◽  
Rule Out

Women with epilepsy constitute about 0.6% of pregnancies. The potential for major structural malformations following gestational exposure to anti-epileptic drugs (AEDs) is well known and causes concern as how best to manage epilepsy during pregnancy. In this review we focus on the structural and functional effects on the developing brain to complement other recent reviews. We do not cover neural tube defects which have been reviewed elsewhere. Suffice to say that carbamazepine, lamotrigine and, in particular, valproate exposure are associated with them. We discuss studies based on animal models as well as those that have followed-up children exposed to AEDs in-utero. Careful longitudinal human research can document the cognitive and behavioural effects, but the long time scales required and inability to rule out confounding variables, both genetic and environmental, are serious limitations. Animal studies are based on the assumption that many developmental processes are conserved between the animals used in the models (most often rodents) and humans. However, the hugely expanded cortex and cognitive and behavioural repertoire of humans implies that there are aspects that can not be well modelled. In addition, due to differences in how susceptible different species are to various teratogens, studies always need to be done in man as well. Nevertheless, an understanding of the molecular mechanisms of neuro-teratogenesis derived from animal models will help us predict which anti-epileptic drugs are likely to cause fewer neuro-developmental problems in humans.

scholarly journals CImP: Cellular Imprinting Proteomics applied to ocular disorders elicited by Congenital Zika virus Syndrome

2019 ◽  
Author(s):  
Livia Rosa-Fernandes ◽  
Raquel Hora Barbosa ◽  
Maria Luiza B. dos Santos ◽  
Claudia B. Angeli ◽  
Thiago P. Silva ◽  
...  
Keyword(s):  
Zika Virus ◽  
Ocular Surface ◽  
Molecular Mechanisms ◽  
Membrane Filter ◽  
Neurological Diseases ◽  
Specific Protein ◽  
Protein Markers ◽  
Impression Cytology ◽  
Zikv Infection ◽  
Molecular Alterations

AbstractIMPORTANCEOcular complications in infants with Congenital Zika Syndrome (CZS) have been reported. However, the molecular mechanisms underlying of eye dysfunctions are presently unknown.OBJECTIVEA method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation.DESIGN, SETTINGS AND PARTICIMPANTSThe CImP method was applied to a cohort divided into three conditions: 1) Ctrl (infants with no infectious diseases, n=5). 2) Zikv (infants exposed to ZIKV gestation, with no microcephaly, n=5). 3) ZikvCZS(infants exposed to ZIKV, with microcephaly, n=3). All conditions were age and sex-matched. An improved impression cytology method was used to capture the outermost ocular surface cells. The number of impression cytology membrane collected was: Ctrl (12), Zikv (14) and ZikvCZS(8). Proteins were extracted and analysed using mass spectrometry-based proteomics technology followed by statistical analysis. Parallel reaction monitoring was performed to validate the expression of specific protein markers.RESULTSUsing the CImP method, 2209 proteins were identified on the membrane-captured conjunctiva epithelial cells. Modulation of neutrophil degranulation, cell death, ocular and neurodevelopment pathways are reported in infants with CZS compared to matched controls. Moreover, the molecular pattern of ocular surface cells retrieved from infants infected during the gestation but with no CZS was different from matched controls.CONCLUSIONS AND PERSPECTIVESMolecular alterations in the ocular cell surface associated to ZIKV infection with and without CZS complications are reported for the first time. We predict that this method will be introduced successfully in the study of several neurological diseases with the aim to identify novel diagnostic and therapeutic biomarkers.

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