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 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 From Mosquito Bites to Sexual Transmission: Evaluating Mouse Models of Zika Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2244
Author(s):  
Elizabeth Balint ◽  
Amelia Montemarano ◽  
Emily Feng ◽  
Ali A. Ashkar
Keyword(s):  
Mouse Models ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Zikv Infection ◽  
Sexually Transmitted ◽  
Advantages And Disadvantages ◽  
Effective Use ◽  
The Impact ◽  
Male To Female

Following the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV. Sexual transmission may broaden the reach of ZIKV infections beyond its current geographical limits, presenting a significant threat worldwide. Several mouse models of ZIKV infection have been developed to investigate ZIKV pathogenesis and develop effective vaccines and therapeutics. However, the majority of these models focus on mosquito-borne infection, while few have considered the impact of sexual transmission on immunity and pathogenesis. This review will examine the advantages and disadvantages of current models of mosquito-borne and sexually transmitted ZIKV and provide recommendations for the effective use of ZIKV mouse models.

scholarly journals Autophagy Contributes to Host Immunity and Protection against Zika Virus Infection via Type I IFN Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yuyi Huang ◽  
Yujie Wang ◽  
Shuhui Meng ◽  
Zhuohang Chen ◽  
Haifan Kong ◽  
...  
Keyword(s):  
Virus Infection ◽  
Cell Line ◽  
Zika Virus ◽  
Fetal Brain ◽  
Host Immunity ◽  
Type I ◽  
Type I Ifn ◽  
Zikv Infection

Recent studies have indicated that the Zika virus (ZIKV) has a significant impact on the fetal brain, and autophagy is contributing to host immune response and defense against virus infection. Here, we demonstrate that ZIKV infection triggered increased LC3 punctuation in mouse monocyte-macrophage cell line (RAW264.7), mouse microglial cell line (BV2), and hindbrain tissues, proving the occurrence of autophagy both in vitro and in vivo. Interestingly, manual intervention of autophagy, like deficiency inhibited by 3-MA, can reduce viral clearance in RAW264.7 cells upon ZIKV infection. Besides, specific siRNA strategy confirmed that autophagy can be activated through Atg7-Atg5 and type I IFN signaling pathway upon ZIKV infection, while knocking down of Atg7 and Atg5 effectively decreased the ZIKV clearance in phagocytes. Furthermore, we analyzed that type I IFN signaling could contribute to autophagic clearance of invaded ZIKV in phagocytes. Taken together, our findings demonstrate that ZIKV-induced autophagy is favorable to activate host immunity, particularly through type I IFN signaling, which participates in host protection and defense against ZIKV infection.

scholarly journals Advances in Zika Virus–Host Cell Interaction: Current Knowledge and Future Perspectives

2019 ◽  
Vol 20 (5) ◽  
pp. 1101 ◽  
Author(s):  
Jae Lee ◽  
Ok Shin
Keyword(s):  
Host Cell ◽  
Zika Virus ◽  
Current Knowledge ◽  
Cell Interaction ◽  
Human Pathogens ◽  
Zikv Infection ◽  
In Vivo Models ◽  
Host Cell Interaction

Emerging mosquito-transmitted RNA viruses, such as Zika virus (ZIKV) and Chikungunya represent human pathogens of an immense global health problem. In particular, ZIKV has emerged explosively since 2007 to cause a series of epidemics in the South Pacific and most recently in the Americas. Although typical ZIKV infections are asymptomatic, ZIKV infection during pregnancy is increasingly associated with microcephaly and other fetal developmental abnormalities. In the last few years, genomic and molecular investigations have established a remarkable progress on the pathogenic mechanisms of ZIKV infection using in vitro and in vivo models. Here, we highlight recent advances in ZIKV-host cell interaction studies, including cellular targets of ZIKV, ZIKV-mediated cell death mechanisms, host cell restriction factors that limit ZIKV replication, and immune evasion mechanisms utilized by ZIKV. Understanding of the mechanisms of ZIKV–host interaction at the cellular level will contribute crucial insights into the development of ZIKV therapeutics and vaccines.

scholarly journals Congenital abnormalities associated with Zika virus infection–Dengue as potential co-factor? A systematic review

2021 ◽  
Vol 15 (1) ◽  
pp. e0008984
Author(s):  
Stephanie Petzold ◽  
Nisreen Agbaria ◽  
Andreas Deckert ◽  
Peter Dambach ◽  
Volker Winkler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Virus Infection ◽  
Dengue Virus ◽  
Protective Effect ◽  
Zika Virus ◽  
Congenital Abnormalities ◽  
Denv Infection ◽  
Current Evidence ◽  
Geographic Variability ◽  
Zikv Infection

Zika virus (ZIKV) emerged in Brazil during 2013–2014 causing an epidemic of previously unknown congenital abnormalities. The frequency of severe congenital abnormalities after maternal ZIKV infection revealed an unexplained geographic variability, especially between the Northeast and the rest of Brazil. Several reasons for this variability have been discussed. Prior immunity against DENV, that affects ZIKV seems to be the most likely explanation. Here we summarise the current evidence regarding the prominent co-factor to potentially explain the geographic variability. This systematic review followed the PRISMA guidelines. The search was conducted up to May 15th, 2020, focussing on immunological interactions from Zika virus with previous Dengue virus infections as potential teratogenic effect for the foetus. Eight out of 339 screened studies reported on the association between ZIKV, prior Dengue virus infection and microcephaly, mostly focusing on antibody-dependent enhancement (ADE) as potential pathomechanism. Prior DENV infection was associated with enhancement for ZIKV infection and increased neurovirulence in one included in vitro study only. Interestingly, the seven in vivo studies exhibited a heterogeneous picture with three studies showing a protective effect of prior DENV infections and others no effect at all. According to several studies, socio-economic factors are associated with increased risk for microcephaly. Very few studies addressed the question of unexplained variability of infection-related microcephaly. Many studies focussed on ADE as mechanism without measuring microcephaly as endpoint. Interestingly, three of the included studies reported a protective effect of prior DENV infection against microcephaly. This systematic review strengthens the hypothesis that immune priming after recent DENV infection is the crucial factor for determining protection or enhancement activity. It is of high importance that the currently ongoing prospective studies include a harmonized assessment of the potential candidate co-factors.

scholarly journals Prior Dengue Virus Infection Is Associated With Increased Viral Load in Patients Infected With Dengue but Not Zika Virus

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Gilberto A Santiago ◽  
Tyler M Sharp ◽  
Eli Rosenberg ◽  
Iris I Sosa Cardona ◽  
Luisa Alvarado ◽  
...  
Keyword(s):  
Viral Load ◽  
Virus Infection ◽  
Dengue Virus ◽  
Zika Virus ◽  
Denv Infection ◽  
T Test ◽  
Viral Rna ◽  
Zikv Infection ◽  
Dengue Virus Infection

Abstract To evaluate potential enhancement of Zika virus (ZIKV) infection among patients with prior dengue virus (DENV) infection, we compared loads of viral RNA among patients infected with ZIKV (n = 1070), DENV-2 (n = 312), or DENV-3 (n = 260). Compared to patients without prior DENV infection, patients with prior DENV infection had significantly higher mean loads of viral RNA if infected with DENV-2 (10.6 vs 11.6 log10 GCE/mL, respectively; t test, P < .0001) or DENV-3 (10.3 vs 10.9 log10 GCE/mL; P < .0001), but not ZIKV (4.7 vs 4.7 log10 GCE/mL; P = .959). These findings provide evidence against in vivo enhancement of ZIKV by anti-DENV antibodies.

scholarly journals Risk of sexually transmitted Zika virus in a cohort of economically disadvantaged urban residents

2021 ◽  
Author(s):  
Juan P Aguilar Ticona ◽  
Huma Baig ◽  
Nivison Nery Jr. ◽  
Simon Doss-Gollin ◽  
Gielson A Sacramento ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Sexually Transmitted Infections ◽  
Zika Virus ◽  
Disease Burden ◽  
Urban Community ◽  
Urban Residents ◽  
Zikv Infection ◽  
Retrospective Survey ◽  
Sexually Transmitted ◽  
Increased Risk

Abstract In order to understand the disease burden of sexually transmitted Zika virus (ZIKV), we prospectively followed a cohort of 359 adult and adolescent residents of an urban community in Salvador, Brazil through the 2015 ZIKV epidemic. Later, in 2017, we used a retrospective survey to associate sexual behavior during the epidemic with ZIKV infection as defined by IgG3-NS1 ELISA. We found that males who engaged in casual sexual encounters during the epidemic were more likely (ORa=6.2; 95%CI 1.2–64.1) to be ZIKV positive, suggesting that specific groups may be at increased risk of sexually transmitted infections.

scholarly journals Neuromuscular Development and Disease: Learning From in vitro and in vivo Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Zachary Fralish ◽  
Ethan M. Lotz ◽  
Taylor Chavez ◽  
Alastair Khodabukus ◽  
Nenad Bursac
Keyword(s):  
Skeletal Muscle ◽  
Cell Culture ◽  
Animal Models ◽  
Schwann Cells ◽  
Motor Neurons ◽  
Small Animal ◽  
In Vivo Models ◽  
Small Animal Models

The neuromuscular junction (NMJ) is a specialized cholinergic synaptic interface between a motor neuron and a skeletal muscle fiber that translates presynaptic electrical impulses into motor function. NMJ formation and maintenance require tightly regulated signaling and cellular communication among motor neurons, myogenic cells, and Schwann cells. Neuromuscular diseases (NMDs) can result in loss of NMJ function and motor input leading to paralysis or even death. Although small animal models have been instrumental in advancing our understanding of the NMJ structure and function, the complexities of studying this multi-tissue system in vivo and poor clinical outcomes of candidate therapies developed in small animal models has driven the need for in vitro models of functional human NMJ to complement animal studies. In this review, we discuss prevailing models of NMDs and highlight the current progress and ongoing challenges in developing human iPSC-derived (hiPSC) 3D cell culture models of functional NMJs. We first review in vivo development of motor neurons, skeletal muscle, Schwann cells, and the NMJ alongside current methods for directing the differentiation of relevant cell types from hiPSCs. We further compare the efficacy of modeling NMDs in animals and human cell culture systems in the context of five NMDs: amyotrophic lateral sclerosis, myasthenia gravis, Duchenne muscular dystrophy, myotonic dystrophy, and Pompe disease. Finally, we discuss further work necessary for hiPSC-derived NMJ models to function as effective personalized NMD platforms.

scholarly journals The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Amelia K. Pinto ◽  
Mariah Hassert ◽  
Xiaobing Han ◽  
Douglas Barker ◽  
Trevor Carnelley ◽  
...  
Keyword(s):  
Virus Infection ◽  
Polyclonal Antibody ◽  
Zika Virus ◽  
Virus Disease ◽  
Polyclonal Antibodies ◽  
Antibody Therapeutics ◽  
The World ◽  
Flavivirus Infection

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease. Three IVIGs (ZIKV-IG, Control-Ig and Gamunex®) were evaluated for their ability to neutralize and/or enhance Zika, dengue 2 and 3 viruses in vitro. The balance between virus neutralization and enhancement provided by the in vitro neutralization data was used to predict the IVIG concentrations which could protect or enhance Zika, and dengue 2 disease in vivo. Using this approach, we were able to define the unique in vivo dynamics of complex polyclonal antibodies, allowing for both enhancement and protection from flavivirus infection. Our results provide a novel understanding of how polyclonal antibodies interact with viruses with implications for the use of polyclonal antibody therapeutics and the development and evaluation of the next generation flavivirus vaccines.

A Novel Peptide Aldehyde with Activity against Human Cytomegalovirus in Two Different in Vivo Models

2000 ◽  
Vol 11 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Olaf Weber ◽  
Jürgen Reefschläger ◽  
Helga Rübsamen-Waigmann ◽  
Siegfried Raddatz ◽  
Matthias Hesseling ◽  
...  
Keyword(s):  
Animal Models ◽  
Antiviral Activity ◽  
Clinical Isolate ◽  
Human Cytomegalovirus ◽  
Murine Cytomegalovirus ◽  
Human Tissues ◽  
In Vivo Models ◽  
Peptide Aldehydes

Novel peptide aldehydes (PAs) were identified as potent inhibitors of human cytomegalovirus (HCMV) in vitro. Although these compounds were highly effective against HCMV, they did not exhibit any activity against murine cytomegalovirus (MCMV). The purpose of this study was to test the antiviral activity of PA 8 as a representative of this novel class of inhibitors against HCMV in vivo. Because of the strict species specificity of HCMV we had to use two artificial animal models. In the first model, HCMV-infected human cells were entrapped into agarose plugs and transplanted into mice. In the second model, SCID mice were transplanted with human tissues that were subsequently infected with a clinical isolate of HCMV. In these two models the antiviral activity of PA 8 was clearly demonstrated, ganciclovir only being slightly superior in its in vivo antiviral activity.

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