A Mouse Model of Zika Virus Pathogenesis

doi:10.1016/J.CHOM.2016.03.010

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A Mouse Model of Zika Virus Pathogenesis

Journal Article•DOI•

A Mouse Model of Zika Virus Pathogenesis

Helen M. Lazear¹, Jennifer Govero², Amber M. Smith², Derek J. Platt², Estefania Fernandez², Jonathan J. Miner², Michael S. Diamond - Show less +3 more•Institutions (2)

University of North Carolina at Chapel Hill¹, Washington University in St. Louis²

11 May 2016-Cell Host & Microbe (Cell Host Microbe)-Vol. 19, Iss: 5, pp 720-730

TL;DR: Ifnar1(-/-) mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses and valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.

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About: This article is published in Cell Host & Microbe.The article was published on 2016-05-11 and is currently open access. It has received 774 citations till now. The article focuses on the topics: Sexual transmission.

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Journal Article•DOI•

Immunogenic cell death in cancer and infectious disease

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Lorenzo Galluzzi¹, Aitziber Buqué, Oliver Kepp, Laurence Zitvogel², Guido Kroemer - Show less +1 more•Institutions (2)

Cornell University¹, Institut Gustave Roussy²

01 Feb 2017-Nature Reviews Immunology

TL;DR: Current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance are reviewed.

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Abstract: Immunogenicity depends on two key factors: antigenicity and adjuvanticity. The presence of exogenous or mutated antigens explains why infected cells and malignant cells can initiate an adaptive immune response provided that the cells also emit adjuvant signals as a consequence of cellular stress and death. Several infectious pathogens have devised strategies to control cell death and limit the emission of danger signals from dying cells, thereby avoiding immune recognition. Similarly, cancer cells often escape immunosurveillance owing to defects in the molecular machinery that underlies the release of endogenous adjuvants. Here, we review current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance.

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1,775 citations

Journal Article•DOI•

Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure

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Xuyu Qian¹, Ha Nam Nguyen¹, Mingxi M. Song¹, Christopher Hadiono¹, Sarah C. Ogden², Christy Hammack², Bing Yao³, Gregory R. Hamersky¹, Fadi Jacob¹, Chun Zhong¹, Ki Jun Yoon¹, William J. Jeang¹, Li Lin³, Yujing Li³, Jai Thakor¹, Daniel A. Berg¹, Ce Zhang¹, Eunchai Kang¹, Michael Chickering¹, David W. Nauen¹, Cheng-Ying Ho⁴, Cheng-Ying Ho⁵, Zhexing Wen¹, Kimberly M. Christian¹, Pei Yong Shi⁶, Brady J. Maher¹, Hao Wu³, Peng Jin³, Hengli Tang², Hongjun Song, Guo Li Ming - Show less +27 more•Institutions (6)

Johns Hopkins University School of Medicine¹, Florida State University², Emory University³, Children's National Medical Center⁴, George Washington University⁵, University of Texas Medical Branch⁶

19 May 2016-Cell

TL;DR: A miniaturized spinning bioreactor (SpinΩ) is developed to generate forebrain-specific organoids from human iPSCs that recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer.

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1,526 citations

Cites background from "A Mouse Model of Zika Virus Pathoge..."

...Two recent studies have shown few differences between properties of different ZIKV strains in different models (Bayer et al., 2016; Lazear et al., 2016)....
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Journal Article•DOI•

Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise.

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Jonathan J. Miner¹, Bin Cao¹, Jennifer Govero¹, Amber M. Smith¹, Estefania Fernandez¹, Omar H. Cabrera¹, Charise Garber¹, Michelle Noll¹, Robyn S. Klein, Kevin K. Noguchi¹, Indira U. Mysorekar¹, Michael S. Diamond - Show less +8 more•Institutions (1)

Washington University in St. Louis¹

19 May 2016-Cell

TL;DR: These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations and to identify ZikV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route.

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713 citations

Cites background or methods or result from "A Mouse Model of Zika Virus Pathoge..."

...Since the type I interferon (IFN) response prevents efficient replication of ZIKV in peripheral organs of WT mice (Lazear et al., 2016), we initially used Ifnar1 / mice to facilitate high levels of ZIKV replication during pregnancy....
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...As expected from prior studies with Ifnar1 / males (Lazear et al., 2016; Rossi et al., 2016), high levels of ZIKV were present in the blood, spleen, and brain of Ifnar1 / dams at day 7 after infection (Figures 1I–1K)....
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...ZIKV has been found in human semen (Musso et al., 2015) and mouse testes (Lazear et al., 2016; Rossi et al., 2016) and can be transmitted sexually frommale to female in humans (Musso et al., 2015)....
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..., 2015) and mouse testes (Lazear et al., 2016; Rossi et al., 2016) and can be transmitted sexually frommale to female in humans (Musso et al....
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...In a complementary approach usingWTmice treated with a blocking anti-ifnar antibody (MAR1-5A3), we reported a less severemodel of ZIKV pathogenesis that also resulted in replication of ZIKV in several organs (Lazear et al., 2016)....
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Journal Article•DOI•

Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection

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Karin Stettler, Martina Beltramello, Diego A. Espinosa¹, Victoria A. Graham², Antonino Cassotta³, Antonino Cassotta⁴, Siro Bianchi, Fabrizia Vanzetta, Andrea Minola, Stefano Jaconi, Federico Mele³, Mathilde Foglierini³, Mattia Pedotti³, Luca Simonelli³, Stuart D. Dowall², Barry Atkinson², Elena Percivalle, Cameron P. Simmons⁵, Cameron P. Simmons⁶, Luca Varani³, Johannes Blum⁷, Johannes Blum⁸, Fausto Baldanti, Elisabetta Cameroni, Roger Hewson², Eva Harris¹, Antonio Lanzavecchia³, Antonio Lanzavecchia⁴, Federica Sallusto³, Davide Corti - Show less +26 more•Institutions (8)

University of California, Berkeley¹, Public Health England², University of Lugano³, ETH Zurich⁴, University of Oxford⁵, University of Melbourne⁶, Swiss Tropical and Public Health Institute⁷, University of Basel⁸

19 Aug 2016-Science

TL;DR: The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus, and an EDIII-targeted antibody protected mice against lethal infection, illustrating the potential for antibody-based therapy.

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Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. By characterizing memory lymphocytes from ZIKV-infected patients, we dissected ZIKV-specific and DENV–cross-reactive immune responses. Antibodies to nonstructural protein 1 (NS1) were largely ZIKV-specific and were used to develop a serological diagnostic tool. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, although poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Memory T cells against NS1 or E proteins were poorly cross-reactive, even in donors preexposed to DENV. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.

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679 citations

Journal Article•DOI•

Modified mRNA Vaccines Protect against Zika Virus Infection.

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Justin M. Richner¹, Sunny Himansu, Kimberly A. Dowd², Scott L. Butler, Vanessa Salazar¹, Julie M. Fox¹, Justin G. Julander³, William W. Tang⁴, Sujan Shresta⁴, Theodore C. Pierson², Giuseppe Ciaramella, Michael S. Diamond - Show less +8 more•Institutions (4)

Washington University in St. Louis¹, National Institutes of Health², Utah State University³, La Jolla Institute for Allergy and Immunology⁴

09 Mar 2017-Cell

TL;DR: A modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of sensitizing individuals to subsequent exposure to DENV, should this become a clinically relevant concern.

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666 citations

Cites methods or result from "A Mouse Model of Zika Virus Pathoge..."

..., 2016), some of these studies used immunocompetent strains for challenge, which do not support as efficient ZIKV infection due to a species-specific lack of antagonism of IFN signaling (Grant et al., 2016; Kumar et al., 2016; Lazear et al., 2016)....
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...Pl aque assays were performed as described previously (Brien et al., 2013; Lazear et al., 2016) For FRNT assays, cells were overlaid with 1% (w/v) methylcellulose in MEM supplemented with 4% heat-inactivated FBS....
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...Virus stocks were propagated in mycoplasma-free Vero cells and titrated by focus-forming assay (FFA), as described previously (Lazear et al., 2016)....
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...…were added to Vero cell monolayers in 96-well plates for 60 min at 37 C. Plaque assays were performed as described previously (Brien et al., 2013; Lazear et al., 2016) For FRNT assays, cells were overlaid with 1% (w/v) methylcellulose in MEM supplemented with 4% heat-inactivated FBS. Plates were…...
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...…et al., 2016), some of these studies used Cell 168, 1114–1125, March 9, 2017 1121 immunocompetent strains for challenge, which do not support as efficient ZIKV infection due to a species-specific lack of antagonism of IFN signaling (Grant et al., 2016; Kumar et al., 2016; Lazear et al., 2016)....
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References

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Journal Article•DOI•

Zika virus outbreak on Yap Island, Federated States of Micronesia.

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Mark R. Duffy¹, Tai-Ho Chen¹, W. Thane Hancock, Ann M. Powers, Jacob L. Kool, Robert S. Lanciotti, Moses Pretrick, Maria Marfel, Stacey Holzbauer, Christine Dubray, Laurent Guillaumot², Anne Griggs, Martin Bel, Amy J. Lambert, Janeen Laven, Olga I. Kosoy, Amanda J. Panella, Brad J. Biggerstaff, Marc Fischer, Edward B. Hayes - Show less +16 more•Institutions (2)

Centers for Disease Control and Prevention¹, Pasteur Institute²

10 Dec 2009-The New England Journal of Medicine

TL;DR: This outbreak of Zika virus illness in Micronesia represents transmission of Zikairus outside Africa and Asia and clinicians and public health officials should be aware of the risk of further expansion of Zika viruses transmission.

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Abstract: BACKGROUND In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. METHODS We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. RESULTS We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. CONCLUSIONS This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.

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2,717 citations

"A Mouse Model of Zika Virus Pathoge..." refers background in this paper

...Typically, ZIKV infection has been associated with a self-limiting febrile illness often including rash, arthralgia, and conjunctivitis, though most infections are asymptomatic (Brasil et al., 2016; Duffy et al., 2009; Hayes, 2009)....
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Journal Article•DOI•

Zika Virus Associated with Microcephaly

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Jernej Mlakar¹, Miša Korva¹, Mateja Poljšak-Prijatelj¹, Jerica Mraz¹, Marko Kolenc¹, Katarina Resman Rus¹, Tina Vesnaver Vipotnik¹, Vesna Fabjan¹, Alenka Vizjak¹, Miroslav Petrovec¹ - Show less +6 more•Institutions (1)

University of Ljubljana¹

10 Feb 2016-The New England Journal of Medicine

TL;DR: The case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil and revealed microcephaly with calcifications in the fetal brain and placenta is described.

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Abstract: Summary A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reversetranscriptase–polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.

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2,403 citations

"A Mouse Model of Zika Virus Pathoge..." refers background in this paper

...of ZIKV RNA, full-length viral genome, or viral particles in the amniotic fluid or brains of fetuses diagnosed with microcephaly, as well as ZIKV IgM in amniotic fluid, consistent with fetal infection (Calvet et al., 2016; Martines et al., 2016; Mlakar et al., 2016; Oliveira Melo et al., 2016; Petersen et al., 2016)....
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...Evidence from infants and fetuses infected in utero suggests ZIKV may be neurotropic (Mlakar et al., 2016; Sarno et al., 2016), and a recent report demonstrated ZIKV infection in human neuroprogenitor cells in culture (Tang et al....
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...By 6 days after infection, high levels of ZIKV viral RNA were observed in CNS tissues of Ifnar1 / mice (> 10 FFU equivalents per gram in the brain and spinal cord), confirming the neurotropic potential of the virus (Bell et al., 1971; Martines et al., 2016; Mlakar et al., 2016; Sarno et al., 2016; Tang et al., 2016)....
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Journal Article•DOI•

Zika Virus (I). Isolations and serological specificity

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G. W. A. Dick¹, S. F. Kitchen², A. J. Haddow²•Institutions (2)

National Institute for Medical Research¹, Rockefeller Foundation²

01 Sep 1952-Transactions of The Royal Society of Tropical Medicine and Hygiene

TL;DR: Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus.

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Abstract: 1. (1) The isolation of what is believed to be a hitherto unrecorded virus is described. The first isolation was made in April 1947 from the serum of a pyrexial rhesus monkey caged in the canopy of Zika Forest. The second isolation was made from a lot of A. africanus taken in January, 1948, in the same forest. The virus has been called Zika virus after the locality from where the isolations were made. 2. (2) Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus. Neutralization tests with Zika virus and the antisera of some other viruses which are neurotropic in mice gave no evidence of any identity of these with Zika virus.

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2,338 citations

Journal Article•DOI•

Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007

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Robert S. Lanciotti¹, Olga Kosoy¹, Janeen Laven¹, Jason O. Velez¹, Amy J. Lambert¹, Alison J. Johnson¹, Stephanie M. Stanfield¹, Mark R. Duffy¹ - Show less +4 more•Institutions (1)

Centers for Disease Control and Prevention¹

01 Aug 2008-Emerging Infectious Diseases

TL;DR: The full coding region nucleic acid sequence and serologic properties of the virus were identified and the virus was identified as Crimean-Congo-Wales coronavirus.

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Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.

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1,944 citations

"A Mouse Model of Zika Virus Pathoge..." refers background or methods in this paper

...A previously published primer set was used to detect ZIKV RNA (Lanciotti et al., 2008): forward, 50-CCGCTGCCCAACACAAG-30; reverse, 50-CCAC TAACGTTCTTTTGCAGACAT-30; probe, 50-/56-FAM/AGCCTACCT/ZEN/TGA CAAGCAATCAGACACTCAA/3IABkFQ/-30 (Integrated DNA Technologies)....
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...Within the mosquito-borne clade of flaviviruses, ZIKV is a member of the Spondweni group; both genetically and serologically, ZIKV is related closely to the four serotypes of DENV with approximately 43% amino acid identity and extensive antibody cross-reactivity (Alkan et al., 2015; Lanciotti et al., 2008)....
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Journal Article•DOI•

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

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Van-Mai Cao-Lormeau, Alexandre Blake¹, Sandrine Mons, Stéphane Lastère, Claudine Roche, Jessica Vanhomwegen¹, Timothée Dub¹, Laure Baudouin, Anita Teissier, P. Larre, Anne-Laure Vial, Christophe Decam, Valérie Choumet¹, Susan K. Halstead², Hugh J. Willison², Lucile Musset, Jean-Claude Manuguerra¹, Philippe Desprès, Emmanuel Fournier, Henri-Pierre Mallet, Didier Musso, Arnaud Fontanet³, Arnaud Fontanet¹, Jean Neil, Frédéric Ghawché - Show less +21 more•Institutions (3)

Pasteur Institute¹, University of Glasgow², Conservatoire national des arts et métiers³

09 Apr 2016-The Lancet

TL;DR: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome, and because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillay-B Barré syndrome.

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1,925 citations

"A Mouse Model of Zika Virus Pathoge..." refers background in this paper

..., 2014), which was associated with a 20-fold increase in cases of Guillain-Barré syndrome (GBS) (Cao-Lormeau et al., 2016; Oehler et al., 2014)....
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