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Cell Host & Microbe

Melanie Schirmer, Lee Denson, Hera Vlamakis, Eric A Franzosa, Sonia Thomas, Nathan M Gotman, Paul Rufo, Susan S Baker, Cary Sauer, James Markowitz, Marian Pfefferkorn, Maria Oliva-Hemker, Joel Rosh, Anthony Otley, Brendan Boyle, David Mack, Robert Baldassano, David Keljo, Neal LeLeiko, Melvin Heyman, Anne Griffiths, Ashish S Patel, Joshua Noe, Subra Kugathasan, Thomas Walters, Curtis Huttenhower, Jeffrey Hyams, Ramnik J Xavier
Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies...
October 10, 2018: Cell Host & Microbe
Haoqing Wang, Christopher O Barnes, Zhi Yang, Michel C Nussenzweig, Pamela J Bjorkman
HIV-1 Env, a trimer of gp120-gp41 heterodimers, mediates membrane fusion after binding host receptor CD4. Receptor binding displaces V1V2 loops from Env's apex, allowing coreceptor binding and opening Env to enable gp41-mediated fusion. We present 3.54 Å and 4.06 Å cryoelectron microscopy structures of partially open soluble native-like Env trimers (SOSIPs) bound to CD4. One structure, a complex with a coreceptor-mimicking antibody that binds both CD4 and gp120, stabilizes the displaced V1V2 and reveals its structure...
October 10, 2018: Cell Host & Microbe
Nicholas C Wu, Seiya Yamayoshi, Mutsumi Ito, Ryuta Uraki, Yoshihiro Kawaoka, Ian A Wilson
Discovery and characterization of broadly neutralizing antibodies (bnAbs) to the influenza hemagglutinin (HA) stem have provided insights for the development of a universal flu vaccine. Identification of signature features common to bnAbs from different individuals will be key to guiding immunogen design. S9-3-37 is a bnAb isolated from a healthy H5N1 vaccinee. Here, structural characterization reveals that the D3-9 gene segment of S9-3-37 contributes most of the interaction surface with the highly conserved stem epitope on HA...
October 10, 2018: Cell Host & Microbe
Arabinda Nayak, Dong Young Kim, Michael J Trnka, Craig H Kerr, Peter V Lidsky, David J Stanley, Brianna Monique Rivera, Kathy H Li, Alma L Burlingame, Eric Jan, Judith Frydman, John D Gross, Raul Andino
The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2 binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies...
October 10, 2018: Cell Host & Microbe
Eric M Walton, Mark R Cronan, C J Cambier, Andrea Rossi, Michele Marass, Matthew D Foglia, W Jared Brewer, Kenneth D Poss, Didier Y R Stainier, Carolyn R Bertozzi, David M Tobin
Mycobacterial infection leads to the formation of characteristic immune aggregates called granulomas, a process accompanied by dramatic remodeling of the host vasculature. As granuloma angiogenesis favors the infecting mycobacteria, it may be actively promoted by bacterial determinants during infection. Using Mycobacterium marinum-infected zebrafish as a model, we identify the enzyme proximal cyclopropane synthase of alpha-mycolates (PcaA) as an important bacterial determinant of granuloma-associated angiogenesis...
October 10, 2018: Cell Host & Microbe
Won Ho Yang, Douglas M Heithoff, Peter V Aziz, Benjamin Haslund-Gourley, Julia S Westman, Sonoko Narisawa, Anthony B Pinkerton, José Luis Millán, Victor Nizet, Michael J Mahan, Jamey D Marth
Sepsis is a life-threatening inflammatory syndrome accompanying a bloodstream infection. Frequently secondary to pathogenic bacterial infections, sepsis remains difficult to treat as a singular disease mechanism. We compared the pathogenesis of murine sepsis experimentally elicited by five bacterial pathogens and report similarities among host responses to Gram-negative Salmonella and E. coli. We observed that a host protective mechanism involving de-toxification of lipopolysaccharide by circulating alkaline phosphatase (AP) isozymes was incapacitated during sepsis caused by Salmonella or E...
October 10, 2018: Cell Host & Microbe
Xuping Xie, Dieudonné B Kum, Hongjie Xia, Huanle Luo, Chao Shan, Jing Zou, Antonio E Muruato, Daniele B A Medeiros, Bruno T D Nunes, Kai Dallmeier, Shannan L Rossi, Scott C Weaver, Johan Neyts, Tian Wang, Pedro F C Vasconcelos, Pei-Yong Shi
Zika virus (ZIKV) infection of the mother during pregnancy causes devastating Zika congenital syndrome in the offspring. A ZIKV vaccine with optimal safety and immunogenicity for use in pregnant women is critically needed. Toward this goal, we have developed a single-dose live-attenuated vaccine candidate that infects cells with controlled, limited infection rounds. The vaccine contains a 9-amino-acid deletion in the viral capsid protein and replicates to titers of > 106 focus-forming units (FFU)/mL in cells expressing the full-length capsid protein...
October 10, 2018: Cell Host & Microbe
Asaf Levy, Jonathan M Conway, Jeffery L Dangl, Tanja Woyke
There is a growing appreciation for the important roles microorganisms play in association with plants. Microorganisms are drawn to distinct plant surfaces by the nutrient-rich microenvironment, and in turn some of these colonizing microbes provide mutualistic benefits to their host. The development of plant probiotics to increase crop yield and provide plant resistance against biotic and abiotic stresses, while minimizing chemical inputs, would benefit from a deeper mechanistic understanding of plant-microbe interaction...
October 10, 2018: Cell Host & Microbe
Cambrian Y Liu, D Brent Polk
Pediatric ulcerative colitis incidence is rapidly rising, yet improved prognostic and therapeutic strategies are needed. In this issue of Cell Host & Microbe, Schirmer et al. (2018) reveal the dynamism of pediatric patient microbiomes through initial diagnosis and treatments, providing insights into microbial targets that predict therapeutic response and disease outcomes.
October 10, 2018: Cell Host & Microbe
Jessica Crothers, Lynn Bry
Microbial activities of gut commensals have been linked to several host diseases. In recent work, Roberts et al. (2018) develop therapeutics targeting microbial production of the metabolite trimethylamine (TMA), which has been linked to cardiovascular disease. This microbiota-based approach holds promise for efficacious therapies that may also reduce host side effects.
October 10, 2018: Cell Host & Microbe
Bernhard C Lechtenberg, Andrew Routh
Viruses employ intricate means to evade host innate immune systems. In this issue of Cell Host & Microbe, Nayak et al. (2018) demonstrate that the cricket paralysis virus (CrPV) protein CrPV-1A blocks host defense through a dual mechanism: directly inhibiting Argonaute2 (Ago2) and simultaneously targeting Ago2 for proteasomal degradation.
October 10, 2018: Cell Host & Microbe
Meri Uusi-Mäkelä, Mika Rämet
In this issue of Cell Host & Microbe, Walton et al. (2018) uncover the mycobacterial factors that activate VEGF signaling and promote aberrant angiogenesis in the tuberculous granuloma. Preventing abnormal angiogenesis in the granuloma represents a potential therapeutic approach for tuberculosis.
October 10, 2018: Cell Host & Microbe
Marit Lingemann, Stefan Taube
Three recent papers highlight the impact of an entry receptor on murine norovirus pathogenesis. CD300lf was shown to be the first proteinaceous entry receptor for a norovirus, specialized intestinal epithelial cells constitute the reservoir for persistence, and a new link between the receptor and a lipid biosynthetic enzyme was revealed.
October 10, 2018: Cell Host & Microbe
Pontus Orning, Trude H Flo, Egil Lien
Early detection of microbial patterns is a hallmark of innate immunity and essential for clearance of invading pathogens. A recent Nature publication by Zhou et al. (2018) has uncovered ALPK1 as a pattern recognition receptor for Gram-negative bacteria triggering NF-κB activation and identified the bacterial sugar ADP-Hep as its ligand.
October 10, 2018: Cell Host & Microbe
Daniel J Sheward, Jinny Marais, Valerie Bekker, Ben Murrell, Kemal Eren, Jinal N Bhiman, Molati Nonyane, Nigel Garrett, Zenda L Woodman, Quarraisha Abdool Karim, Salim S Abdool Karim, Lynn Morris, Penny L Moore, Carolyn Williamson
Eliciting antibodies that neutralize a broad range of circulating HIV strains (broadly neutralizing antibodies [bnAbs]) represents a key priority for vaccine development. HIV superinfection (re-infection with a second strain following an established infection) has been associated with neutralization breadth, and can provide insights into how the immune system responds to sequential exposure to distinct HIV envelope glycoproteins (Env). Characterizing the neutralizing antibody (nAb) responses in four superinfected women revealed that superinfection does not boost memory nAb responses primed by the first infection or promote nAb responses to epitopes conserved in both infecting viruses...
October 10, 2018: Cell Host & Microbe
Pierre M Jean Beltran, Katelyn C Cook, Yutaka Hashimoto, Cyril Galitzine, Laura A Murray, Olga Vitek, Ileana M Cristea
Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism. Here, we discovered that the enveloped viruses human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) induce the biogenesis of and unique morphological changes to peroxisomes to support their replication...
October 10, 2018: Cell Host & Microbe
Jianzhong Shi, Guohua Deng, Shujie Ma, Xianying Zeng, Xin Yin, Mei Li, Bo Zhang, Pengfei Cui, Yan Chen, Huanliang Yang, Xiaopeng Wan, Liling Liu, Pucheng Chen, Yongping Jiang, Yuntao Guan, Jinxiong Liu, Wenli Gu, Shuyu Han, Yangming Song, Libin Liang, Zhiyuan Qu, Yujie Hou, Xiurong Wang, Hongmei Bao, Guobin Tian, Yanbing Li, Li Jiang, Chengjun Li, Hualan Chen
H7N9 low pathogenic influenza viruses emerged in China in 2013 and mutated to highly pathogenic strains in 2017, resulting in human infections and disease in chickens. To control spread, a bivalent H5/H7 inactivated vaccine was introduced in poultry in September 2017. To monitor virus evolution and vaccine efficacy, we collected 53,884 poultry samples across China from February 2017 to January 2018. We isolated 252 H7N9 low pathogenic viruses, 69 H7N9 highly pathogenic viruses, and one H7N2 highly pathogenic virus, of which two low pathogenic and 14 highly pathogenic strains were collected after vaccine introduction...
October 10, 2018: Cell Host & Microbe
Pei-Chung Lee, Matthias P Machner
The intracellular pathogen Legionella pneumophila encodes translocated effector proteins that modify host cell processes to support bacterial survival and growth. Here, we show that the L. pneumophila effector protein LegK7 hijacks the conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase (MST1 in mammals), which is the key regulator of pathway activation. LegK7, like Hippo/MST1, phosphorylates the scaffolding protein MOB1, which triggers a signaling cascade resulting in the degradation of the transcriptional regulators TAZ and YAP1...
September 12, 2018: Cell Host & Microbe
Meixiang Zhang, Yi-Hsuan Chiang, Tania Y Toruño, DongHyuk Lee, Miaomiao Ma, Xiangxiu Liang, Neeraj K Lal, Mark Lemos, Yi-Ju Lu, Shisong Ma, Jun Liu, Brad Day, Savithramma P Dinesh-Kumar, Katayoon Dehesh, Daolong Dou, Jian-Min Zhou, Gitta Coaker
Microbial patterns are recognized by cell-surface receptors to initiate pattern-triggered immunity (PTI) in plants. Receptor-like cytoplasmic kinases (RLCKs), such as BIK1, and calcium-dependent protein kinases (CPKs) are engaged during PTI to activate the NADPH oxidase RBOHD for reactive oxygen species (ROS) production. It is unknown whether protein kinases besides CPKs and RLCKs participate in RBOHD regulation. We screened mutants in all ten Arabidopsis MAP4 kinases (MAP4Ks) and identified the conserved MAP4K SIK1 as a positive regulator of PTI...
September 12, 2018: Cell Host & Microbe
Agnieszka D Truax, Liang Chen, Jason W Tam, Ning Cheng, Hao Guo, A Alicia Koblansky, Wei-Chun Chou, Justin E Wilson, W June Brickey, Alex Petrucelli, Rongrong Liu, Daniel E Cooper, Mark J Koenigsknecht, Vincent B Young, Mihai G Netea, Rinke Stienstra, R Balfour Sartor, Stephanie A Montgomery, Rosalind A Coleman, Jenny P-Y Ting
In addition to high-fat diet (HFD) and inactivity, inflammation and microbiota composition contribute to obesity. Inhibitory immune receptors, such as NLRP12, dampen inflammation and are important for resolving inflammation, but their role in obesity is unknown. We show that obesity in humans correlates with reduced expression of adipose tissue NLRP12. Similarly, Nlrp12-/- mice show increased weight gain, adipose deposition, blood glucose, NF-κB/MAPK activation, and M1-macrophage polarization. Additionally, NLRP12 is required to mitigate HFD-induced inflammasome activation...
September 12, 2018: Cell Host & Microbe
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