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https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#1
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29144463/a-single-cell-survey-of-the-small-intestinal-epithelium
#2
Adam L Haber, Moshe Biton, Noga Rogel, Rebecca H Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M Delorey, Michael R Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J Xavier, Aviv Regev
Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29119608/synthetic-aav-crispr-vectors-for-blocking-hiv-1-expression-in-persistently-infected-astrocytes
#3
Christine Kunze, Kathleen Börner, Eike Kienle, Tanja Orschmann, Ejona Rusha, Martha Schneider, Milena Radivojkov-Blagojevic, Micha Drukker, Sabrina Desbordes, Dirk Grimm, Ruth Brack-Werner
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29096712/crosstalk-between-h9n2-avian-influenza-virus-and-crypt-derived-intestinal-organoids
#4
Lulu Huang, Qihang Hou, Lulu Ye, Qian Yang, Qinghua Yu
The spread of Avian influenza virus via animal feces makes the virus difficult to prevent, which causes great threat to human health. Therefore, it is imperative to understand the survival and invasion mechanism of H9N2 virus in the intestinal mucosa. In this study, we used mouse threedimensional intestinal organoids that contained intestinal crypts and villi differentiated from intestinal stem cells to explore interactions between H9N2 avian influenza virus and the intestinal mucosa. The HA, NA, NP and PB1 genes of H9N2 viruses could be detected in intestinal organoids at 1 h, and reached peak levels at 48 h post-infection...
November 2, 2017: Veterinary Research
https://www.readbyqxmd.com/read/29080429/consequences-of-congenital-zika-virus-infection
#5
REVIEW
Derek J Platt, Jonathan J Miner
The 2015 Zika virus (ZIKV) epidemic in the Americas led to the discovery that ZIKV causes congenital abnormalities including microcephaly, intrauterine growth restriction, and eye disease that can result in blindness. Studies in animal models and human organoid cultures, together with human epidemiological studies, have shown that ZIKV crosses the placenta and subsequently replicates within fetal tissues including the developing brain. Preferential infection of neural cell precursors causes damage to the developing fetal brain...
October 25, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29020636/self-organized-cerebral-organoids-with-human-specific-features-predict-effective-drugs-to-combat-zika-virus-infection
#6
Momoko Watanabe, Jessie E Buth, Neda Vishlaghi, Luis de la Torre-Ubieta, Jiannis Taxidis, Baljit S Khakh, Giovanni Coppola, Caroline A Pearson, Ken Yamauchi, Danyang Gong, Xinghong Dai, Robert Damoiseaux, Roghiyh Aliyari, Simone Liebscher, Katja Schenke-Layland, Christine Caneda, Eric J Huang, Ye Zhang, Genhong Cheng, Daniel H Geschwind, Peyman Golshani, Ren Sun, Bennett G Novitch
The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28994790/modelling-zika-virus-infection-of-the-developing-human-brain-in-vitro-using-stem-cell-derived-cerebral-organoids
#7
Max R Salick, Michael F Wells, Kevin Eggan, Ajamete Kaykas
The recent emergence of Zika virus (ZIKV) in susceptible populations has led to an abrupt increase in microcephaly and other neurodevelopmental conditions in newborn infants. While mosquitos are the main route of viral transmission, it has also been shown to spread via sexual contact and vertical mother-to-fetus transmission. In this latter case of transmission, due to the unique viral tropism of ZIKV, the virus is believed to predominantly target the neural progenitor cells (NPCs) of the developing brain. Here a method for modeling ZIKV infection, and the resulting microcephaly, that occur when human cerebral organoids are exposed to live ZIKV is described...
September 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28974702/human-intestinal-organoids-express-histo-blood-group-antigens-bind-norovirus-vlps-and-support-limited-norovirus-replication
#8
Dongsheng Zhang, Ming Tan, Weiming Zhong, Ming Xia, Pengwei Huang, Xi Jiang
Through pluripotent stem cell (PSC) technology, human intestinal organoids (HIOs) with remarkably similarity to the fetal intestine in cellular composition, architecture, and absorptive/secretory functions have been successfully developed, providing a useful in vitro model system to study the structure and function of human congenital gut and intestinally related diseases. We report here the usefulness of HIOs as a model system to study intestinal carbohydrate expression, virus-host interaction, and replication of human noroviruses (huNoVs)...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28968863/replication-of-zika-virus-in-human-prostate-cells-a-potential-source-of-sexually-transmitted-virus
#9
Jennifer L Spencer, Anismrita Lahon, Linda L Tran, Ravi P Arya, Alexander R Kneubehl, Megan B Vogt, Daniela Xavier, David R Rowley, Jason T Kimata, Rebecca R Rico-Hesse
Background: While Zika virus (ZIKV) is mainly transmitted by mosquitoes, numerous cases of sexual transmission have been reported during recent outbreaks. Little is known about which host cell types or entry factors aid in mediating this sexual transmission. Methods: In this study, we investigated ZIKV cell tropism by infecting two types of human prostate cells with three contemporary ZIKV isolates from persons infected in the Americas. We utilized qRT-PCR and immunofluorescence to measure infection and flow cytometry to detect entry factor expression...
August 24, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28874392/zika-virus-has-oncolytic-activity-against-glioblastoma-stem-cells
#10
Zhe Zhu, Matthew J Gorman, Lisa D McKenzie, Jiani N Chai, Christopher G Hubert, Briana C Prager, Estefania Fernandez, Justin M Richner, Rong Zhang, Chao Shan, Eric Tycksen, Xiuxing Wang, Pei-Yong Shi, Michael S Diamond, Jeremy N Rich, Milan G Chheda
Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile virus indiscriminately killed both tumor and normal neural cells...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28826723/zika-virus-encoded-ns2a-disrupts-mammalian-cortical-neurogenesis-by-degrading-adherens-junction-proteins
#11
Ki-Jun Yoon, Guang Song, Xuyu Qian, Jianbo Pan, Dan Xu, Hee-Sool Rho, Nam-Shik Kim, Christa Habela, Lily Zheng, Fadi Jacob, Feiran Zhang, Emily M Lee, Wei-Kai Huang, Francisca Rojas Ringeling, Caroline Vissers, Cui Li, Ling Yuan, Koeun Kang, Sunghan Kim, Junghoon Yeo, Yichen Cheng, Sheng Liu, Zhexing Wen, Cheng-Feng Qin, Qingfeng Wu, Kimberly M Christian, Hengli Tang, Peng Jin, Zhiheng Xu, Jiang Qian, Heng Zhu, Hongjun Song, Guo-Li Ming
Zika virus (ZIKV) directly infects neural progenitors and impairs their proliferation. How ZIKV interacts with the host molecular machinery to impact neurogenesis in vivo is not well understood. Here, by systematically introducing individual proteins encoded by ZIKV into the embryonic mouse cortex, we show that expression of ZIKV-NS2A, but not Dengue virus (DENV)-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. Mechanistically, in vitro mapping of protein-interactomes and biochemical analysis suggest interactions between ZIKA-NS2A and multiple adherens junction complex (AJ) components...
September 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28817682/experimental-study-of-tuberculosis-from-animal-models-to-complex-cell-systems-and-organoids
#12
REVIEW
Kaori L Fonseca, Pedro N S Rodrigues, I Anna S Olsson, Margarida Saraiva
Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease. Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant. On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed. On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment. It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host-pathogen interactions during infection, and for that, better experimental models are needed...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28756233/organoid-culture-systems-to-study-host-pathogen-interactions
#13
REVIEW
Devanjali Dutta, Hans Clevers
Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered...
August 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28736217/high-content-screening-in-hpsc-neural-progenitors-identifies-drug-candidates-that-inhibit-zika-virus-infection-in-fetal-like-organoids-and-adult-brain
#14
Ting Zhou, Lei Tan, Gustav Y Cederquist, Yujie Fan, Brigham J Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J Brennand, Qisheng Zhang, Robert E Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28717211/epithelial-cell-specific-raptor-is-required-for-initiation-of-type-2-mucosal-immunity-in-small-intestine
#15
Bola Aladegbami, Lauren Barron, James Bao, Jason Colasanti, Christopher R Erwin, Brad W Warner, Jun Guo
Intestinal tuft cells are one of 4 secretory cell linages in the small intestine and the source of IL-25, a critical initiator of the type 2 immune response to parasite infection. When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in intestinal epithelium via Tamoxifen injection in Tritrichomonas muris (Tm) infected mice, tuft cells, IL-25 in epithelium and IL-13 in the mesenchyme were significantly reduced, but Tm burden was not affected. When Tm infected mice were treated with rapamycin, DCLK1 and IL-25 expression in enterocytes and IL-13 expression in mesenchyme were diminished...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638807/translational-rodent-models-for-research-on-parasitic-protozoa-a-review-of-confounders-and-possibilities
#16
REVIEW
Totta Ehret, Francesca Torelli, Christian Klotz, Amy B Pedersen, Frank Seeber
Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28614372/intestinal-organoids-model-human-responses-to-infection-by-commensal-and-shiga-toxin-producing-escherichia-coli
#17
Sayali S Karve, Suman Pradhan, Doyle V Ward, Alison A Weiss
Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28534760/minibrain-storm-cerebral-organoids-aren-t-real-brains-but-they-provide-a-powerful-platform-for-modeling-brain-diseases-like-zika-infection-alzheimer-s-and-even-autism
#18
Shannon Fischer
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28488235/emulating-host-microbiome-ecosystem-of-human-gastrointestinal-tract-in-vitro
#19
Gun-Seok Park, Min Hee Park, Woojung Shin, Connie Zhao, Sameer Sheikh, So Jung Oh, Hyun Jung Kim
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human...
June 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28484457/type-i-and-type-iii-interferons-display-different-dependency-on-mitogen-activated-protein-kinases-to-mount-an-antiviral-state-in-the-human-gut
#20
Kalliopi Pervolaraki, Megan L Stanifer, Stephanie Münchau, Lynnsey A Renn, Dorothee Albrecht, Stefan Kurzhals, Elena Senís, Dirk Grimm, Jutta Schröder-Braunstein, Ronald L Rabin, Steeve Boulant
Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined...
2017: Frontiers in Immunology
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