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Cell Host Microbe
This journal offers authors two options (open access or subscription) to publish research

Jun 12, 2019

Volume 25Issue 6p767-892
Open Archive
On the cover: Appropriate neutralizing epitope presentation and antigenicity are keys for viral vaccine design. In this issue of Cell Host & Microbe, Yuan et al. (pp. 873–883) show that broadly neutralizing antibody ACS202 penetrates the Env glycan shield to target the conformationally flexible fusion peptide of gp41, which is a site of vulnerability on HIV-1. Wu et al. (pp. 836–844) uncover multiple mutually exclusive pathways for egg adaptation of influenza virus vaccine strains, which may be leveraged to develop more effective H3N2 seasonal vaccines. These structural studies provide insights for vaccine design. Image designed by Meng Yuan, Nicholas Wu, and Ella Maru Studio....
On the cover: Appropriate neutralizing epitope presentation and antigenicity are keys for viral vaccine design. In this issue of Cell Host & Microbe, Yuan et al. (pp. 873–883) show that broadly neutralizing antibody ACS202 penetrates the Env glycan shield to target the conformationally flexible fusion peptide of gp41, which is a site of vulnerability on HIV-1. Wu et al. (pp. 836–844) uncover multiple mutually exclusive pathways for egg adaptation of influenza virus vaccine strains, which may be leveraged to develop more effective H3N2 seasonal vaccines. These structural studies provide insights for vaccine design. Image designed by Meng Yuan, Nicholas Wu, and Ella Maru Studio.

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Articles

  • Resistin-like Molecule α Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin

    • Tamia A. Harris,
    • Sureka Gattu,
    • Daniel C. Propheter,
    • Zheng Kuang,
    • Shai Bel,
    • Kelly A. Ruhn,
    • Andrew L. Chara,
    • Marshall Edwards,
    • Chenlu Zhang,
    • Jay-Hyun Jo,
    • Prithvi Raj,
    • Christos C. Zouboulis,
    • Heidi H. Kong,
    • Julia A. Segre,
    • Lora V. Hooper
    Vitamin A regulates skin immunity via unknown mechanisms. Harris et al. show that RELMα is an antimicrobial protein expressed by epidermal cells that shapes resident skin bacterial communities and limits skin infection. RELMα is induced by dietary vitamin A and mediates vitamin-A-dependent resistance to skin infection.
  • Daily Sampling Reveals Personalized Diet-Microbiome Associations in Humans

    • Abigail J. Johnson,
    • Pajau Vangay,
    • Gabriel A. Al-Ghalith,
    • Benjamin M. Hillmann,
    • Tonya L. Ward,
    • Robin R. Shields-Cutler,
    • Austin D. Kim,
    • Anna Konstantinovna Shmagel,
    • Arzang N. Syed,
    • Personalized Microbiome Class Students,
    • Jens Walter,
    • Ravi Menon,
    • Katie Koecher,
    • Dan Knights
    Dietary intake is often considered to be a driver of microbiome variation. Johnson et al. use longitudinal sampling and daily dietary records to model microbiome changes in response to diet and find that microbiome responses to diet are personalized.
  • Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model

    • Bryan B. Hsu,
    • Travis E. Gibson,
    • Vladimir Yeliseyev,
    • Qing Liu,
    • Lorena Lyon,
    • Lynn Bry,
    • Pamela A. Silver,
    • Georg K. Gerber
    How bacteriophages impact bacterial communities in vivo is unclear. Hsu et al. investigate this in mice carrying a model microbiome. Phage predation directly impacts susceptible bacteria, leading to cascading effects on other bacterial species, with consequences on the gut metabolome. Phages can be harnessed to modulate the microbiome and host.
  • Structural Basis for the Inhibition of CRISPR-Cas12a by Anti-CRISPR Proteins

    • Heng Zhang,
    • Zhuang Li,
    • Courtney M. Daczkowski,
    • Clinton Gabel,
    • Andrew D. Mesecar,
    • Leifu Chang
    CRISPR-Cas12a protects bacteria from bacteriophages but is counteracted by inhibitors. Zhang et al. report cryo-EM structures of Cas12a bound to anti-CRISPR proteins. AcrVA1 binds to Cas12a by mimicking the protospacer-adjacent motif (PAM) of a target DNA and cleaves crRNA to inactivate Cas12a. AcrVA4 prevents conformational changes required for Cas12a activation.
  • Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope

    • Goran Bajic,
    • Max J. Maron,
    • Yu Adachi,
    • Taishi Onodera,
    • Kevin R. McCarthy,
    • Charles E. McGee,
    • Gregory D. Sempowski,
    • Yoshimasa Takahashi,
    • Garnett Kelsoe,
    • Masayuki Kuraoka,
    • Aaron G. Schmidt
    Eliciting protective immunity against influenza remains a major challenge. Bajic et al. show how hemagglutinin (HA) hyperglycosylation can restrict the resulting antibody repertoire to an occluded epitope at the HA head interface. These antibodies protect against influenza-virus challenge, providing insights into antigen engineering to alter antibody responses.
  • Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

    • Nicholas C. Wu,
    • Huibin Lv,
    • Andrew J. Thompson,
    • Douglas C. Wu,
    • Wilson W.S. Ng,
    • Rameshwar U. Kadam,
    • Chih-Wei Lin,
    • Corwin M. Nycholat,
    • Ryan McBride,
    • Weiwen Liang,
    • James C. Paulson,
    • Chris K.P. Mok,
    • Ian A. Wilson
    Wu et al. characterize the incompatibility between two major egg-adaptive mutations in human H3N2 virus hemagglutinin, G186V and L194P, which confer either minimal or significant antigenic change, respectively. This study suggests that the antigenically disruptive mutation L194P that occurs during egg-based influenza vaccine production can be prevented by mutational incompatibility.
  • A Secreted Viral Nonstructural Protein Determines Intestinal Norovirus Pathogenesis

    • Sanghyun Lee,
    • Hejun Liu,
    • Craig B. Wilen,
    • Zoi E. Sychev,
    • Chandni Desai,
    • Barry L. Hykes Jr.,
    • Robert C. Orchard,
    • Broc T. McCune,
    • Ki-Wook Kim,
    • Timothy J. Nice,
    • Scott A. Handley,
    • Megan T. Baldridge,
    • Gaya K. Amarasinghe,
    • Herbert W. Virgin
    Norovirus is an enteric virus that infects intestinal epithelial tuft cells in mice. Lee et al. discover that murine norovirus NS1 is an unconventionally secreted protein that overcomes IFN-λ-mediated norovirus control and is critical for intestinal infection in mice. Additionally, vaccination with NS1 alone confers protection, suggesting potential vaccine strategies.
  • IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation

    • Dominik Hotter,
    • Matteo Bosso,
    • Kasper L. Jønsson,
    • Christian Krapp,
    • Christina M. Stürzel,
    • Atze Das,
    • Elisabeth Littwitz-Salomon,
    • Ben Berkhout,
    • Alina Russ,
    • Sabine Wittmann,
    • Thomas Gramberg,
    • Yue Zheng,
    • Laura J. Martins,
    • Vicente Planelles,
    • Martin R. Jakobsen,
    • Beatrice H. Hahn,
    • Ulf Dittmer,
    • Daniel Sauter,
    • Frank Kirchhoff
    The interferon γ-inducible protein 16 (IFI16) is an immune sensor of retroviral DNA intermediates. Hotter et al. demonstrate that IFI16 suppresses HIV-1 transcription and latency reactivation by interfering with Sp1-dependent gene expression. However, highly prevalent subtype C HIV-1 strains are less susceptible to IFI16 than other subtypes of HIV-1.

Short Articles

  • Conformational Plasticity in the HIV-1 Fusion Peptide Facilitates Recognition by Broadly Neutralizing Antibodies

    • Meng Yuan,
    • Christopher A. Cottrell,
    • Gabriel Ozorowski,
    • Marit J. van Gils,
    • Sonu Kumar,
    • Nicholas C. Wu,
    • Anita Sarkar,
    • Jonathan L. Torres,
    • Natalia de Val,
    • Jeffrey Copps,
    • John P. Moore,
    • Rogier W. Sanders,
    • Andrew B. Ward,
    • Ian A. Wilson
    The HIV-1 Env fusion peptide (FP) is a site of vulnerability targeted by the immune system. Yuan et al. show that broadly neutralizing antibody ACS202 penetrates the Env glycan shield to target the FP. The diverse approach angles to the FP by different neutralizing antibodies provide insights for vaccine design.
  • Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts

    • Hannah M. Rowe,
    • Erik Karlsson,
    • Haley Echlin,
    • Ti-Cheng Chang,
    • Lei Wang,
    • Tim van Opijnen,
    • Stanley B. Pounds,
    • Stacey Schultz-Cherry,
    • Jason W. Rosch
    Rowe et al. conduct a screen to identify pneumococcal genes required for effective transmission in a ferret model. They establish the fitness landscape of S. pneumoniae genes during mammalian transmission and find that maternal vaccination with the identified transmission factors can block bacterial transmission in the offspring.
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