Cell Host & Microbe

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Viral Evasion of Autophagy

Christian Münz

Cell Host & Microbe > 2007 > 1 > 1 > 9-11

Restriction of both bacterial and viral pathogen growth by autophagy has been documented in vitro. In this issue of Cell Host & Microbe, Orvedahl et al. demonstrate for the first time that inhibition of autophagy by a viral gene product is essential for neurovirulence of herpesviruses.

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Rebuilding Host-Pathogen Interaction from the Ground Up: In Vitro Reconstitution of the Inflammasome

Joseph A. Duncan, Jenny Pan-Yun Ting

Cell Host & Microbe > 2007 > 1 > 1 > 7-9

The inflammasome is a macromolecular complex responsible for the proteolytic processing and activation of the secreted cytokine IL-1β. It is assembled and activated in response to upstream intracellular sensors of microbial components and cell injury. Now, Faustin et al. describe an in vitro cell-free reconstitution of the inflammasome, opening up a new avenue to better understand this innate immune...

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Salmonella SPI1 Effector SipA Persists after Entry and Cooperates with a SPI2 Effector to Regulate Phagosome Maturation and Intracellular Replication

Lyndsey C. Brawn, Richard D. Hayward, Vassilis Koronakis

Cell Host & Microbe > 2007 > 1 > 1 > 63-75

Salmonellae employ two type III secretion systems (T3SSs), SPI1 and SPI2, to deliver virulence effectors into mammalian cells. SPI1 effectors, including actin-binding SipA, trigger initial bacterial uptake, whereas SPI2 effectors promote subsequent replication within customized Salmonella-containing vacuoles (SCVs). SCVs sequester actin filaments and subvert microtubule-dependent motors to migrate...

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A Two-Pronged Mechanism for HIV-1 Nef-Mediated Endocytosis of Immune Costimulatory Molecules CD80 and CD86

Ashutosh Chaudhry, Suman Ranjan Das, Shahid Jameel, Anna George, more

Cell Host & Microbe > 2007 > 1 > 1 > 37-49

The Nef protein of HIV-1 mediates immune evasion by relocating major histocompatibility complex (MHC) molecules and the immune costimulatory molecules CD80 and CD86 away from the monocytic cell surface. We describe a two-pronged mechanism by which Nef removes CD80 and CD86 from the cell surface. While MHCI, CD80, and CD86 are all internalized via a dynamin-independent pathway, the endocytic mechanism...

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Bacterial Interference of Ubiquitination and Deubiquitination

Anne Rytkönen, David W. Holden

Cell Host & Microbe > 2007 > 1 > 1 > 13-22

Ubiquitination and deubiquitination regulate several essential cellular processes such as protein degradation, cell-cycle progression, signaling, and DNA repair. Given the importance of these processes, it is not surprising that many microbes have developed the means to interfere with different stages of ubiquitin pathways to promote their survival and replication. This review focuses on virulence...

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HSV-1 ICP34.5 Confers Neurovirulence by Targeting the Beclin 1 Autophagy Protein

Anthony Orvedahl, Diane Alexander, Zsolt Tallóczy, Qihua Sun, more

Cell Host & Microbe > 2007 > 1 > 1 > 23-35

Autophagy is postulated to play a role in antiviral innate immunity. However, it is unknown whether viral evasion of autophagy is important in disease pathogenesis. Here we show that the herpes simplex virus type 1 (HSV-1)-encoded neurovirulence protein ICP34.5 binds to the mammalian autophagy protein Beclin 1 and inhibits its autophagy function. A mutant HSV-1 virus lacking the Beclin 1-binding domain...

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Host-Microbe Interactions: Fulfilling a Niche

B. Brett Finlay, Ruslan Medzhitov

Cell Host & Microbe > 2007 > 1 > 1 > 3-4

The diversity, sophistication, and range of interactions between microbes and their hosts is truly remarkable. With the advent of new technologies to study these varied connections, and a growing appreciation of their importance, this is the ideal time to launch a new journal that will archive these new findings in the field of host-microbe interactions.

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ALIX Catches HIV

Juan Martin-Serrano, Mark Marsh

Cell Host & Microbe > 2007 > 1 > 1 > 5-7

ESCRT and ESCRT-associated proteins are required during the assembly and release of many RNA viruses, including HIV. Two new papers provide structures for the ESCRT-associated protein ALIX/AIP1 and demonstrate how this protein interacts with HIV Gag. One of these studies provides the clearest evidence to date that ESCRT-III mediates key events in virus release and indicates that there are cellular...

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The Broad Antibacterial Activity of the Natural Antibody Repertoire Is Due to Polyreactive Antibodies

Zhao-Hua Zhou, Yahong Zhang, Ya-Fang Hu, Larry M. Wahl, more

Cell Host & Microbe > 2007 > 1 > 1 > 51-61

Polyreactive antibodies bind to a variety of structurally unrelated antigens. The function of these antibodies, however, has remained an enigma, and because of their low binding affinity their biological relevance has been questioned. Using a panel of monoclonal polyreactive antibodies, we showed that these antibodies can bind to both Gram-negative and Gram-positive bacteria and acting through the...

article

The Host-Microbe Interface: A New Voyage of Discovery

Lakshmi Goyal

Cell Host & Microbe > 2007 > 1 > 1 > 1-2

article

Type III Secretion Effectors of the IpaH Family Are E3 Ubiquitin Ligases

John R. Rohde, Ashton Breitkreutz, Alexandre Chenal, Philippe J. Sansonetti, more

Cell Host & Microbe > 2007 > 1 > 1 > 77-83

Many bacteria pathogenic for plants or animals, including Shigella spp., which is responsible for shigellosis in humans, use a type III secretion apparatus to inject effector proteins into host cells. Effectors alter cell signaling and host responses induced upon infection; however, their precise biochemical activities have been elucidated in very few cases. Utilizing Saccharomyces cerevisiae as a...

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A Type III Secretion System in Vibrio cholerae Translocates a Formin/Spire Hybrid-like Actin Nucleator to Promote Intestinal Colonization

Vincent C. Tam, Davide Serruto, Michelle Dziejman, William Brieher, more

Cell Host & Microbe > 2007 > 1 > 2 > 95-107

We have previously characterized a non-O1, non-O139 Vibrio cholerae strain, AM-19226, that lacks the known virulence factors but contains components of a type III secretion system (T3SS). In this study, we demonstrated that the T3SS is functional and is required for intestinal colonization in the infant mouse model. We also identified VopF, which is conserved among T3SS-positive V. cholerae strains,...

article

A Staphylococcus aureus Regulatory System that Responds to Host Heme and Modulates Virulence

Victor J. Torres, Devin L. Stauff, Gleb Pishchany, Jelena S. Bezbradica, more

Cell Host & Microbe > 2007 > 1 > 2 > 109-119

Staphylococcus aureus, a bacterium responsible for tremendous morbidity and mortality, exists as a harmless commensal in approximately 25% of humans. Identifying the molecular machinery activated upon infection is central to understanding staphylococcal pathogenesis. We describe the heme sensor system (HssRS) that responds to heme exposure and activates expression of the heme-regulated transporter...

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A Plasmid-Based Reverse Genetics System for Animal Double-Stranded RNA Viruses

Takeshi Kobayashi, Annukka A.R. Antar, Karl W. Boehme, Pranav Danthi, more

Cell Host & Microbe > 2007 > 1 > 2 > 147-157

Mammalian orthoreoviruses (reoviruses) are highly tractable experimental models for studies of double-stranded (ds) RNA virus replication and pathogenesis. Reoviruses infect respiratory and intestinal epithelium and disseminate systemically in newborn animals. Until now, a strategy to rescue infectious virus from cloned cDNA has not been available for any member of the Reoviridae family of dsRNA viruses...

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HIV-1 Nef Assembles a Src Family Kinase-ZAP-70/Syk-PI3K Cascade to Downregulate Cell-Surface MHC-I

Chien-Hui Hung, Laurel Thomas, Carl E. Ruby, Katelyn M. Atkins, more

Cell Host & Microbe > 2007 > 1 > 2 > 121-133

HIV-1 Nef, which is required for the efficient onset of AIDS, enhances viral replication and infectivity by exerting multiple effects on infected cells. Nef downregulates cell-surface MHC-I molecules by an uncharacterized PI3K pathway requiring the actions of two Nef motifs—EEEE ₆₅ and PXXP ₇₅ . We report that the Nef EEEE ₆₅ targeting motif enables Nef PXXP ₇₅ to bind...

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A Reverse Genetics System for dsRNA Viruses

Ralph S. Baric, Amy C. Sims

Cell Host & Microbe > 2007 > 1 > 2 > 90-91

The advent of a new reverse genetics system for reoviruses, described in this issue of Cell Host & Microbe by Kobayashi et al., opens new horizons of investigation into the molecular mechanisms governing dsRNA virus replication and pathogenesis. The elegant approach for recombinant reovirus recovery from a set of plasmid DNAs provides a template for designing similar reverse genetics systems for...

article

Antibodies to West Nile Virus: A Double-Edged Sword

Per Johan Klasse, Dennis R. Burton

Cell Host & Microbe > 2007 > 1 > 2 > 87-89

Antibodies, although critical for host defense against West Nile virus (WNV), can both neutralize and enhance viral infection. In this issue of Cell Host & Microbe, Pierson et al. dissect these opposing effects and demonstrate that, when 120 epitopes are available per WNV virion, ∼25 are occupied by antibody at 50% neutralization. At lower occupancies, enhancement of infection dominates; at higher...

article

Did Bacterial Sensing of Host Environments Evolve from Sensing within Microbial Communities?

Samuel I. Miller, Lucas R. Hoffman, Sarah Sanowar

Cell Host & Microbe > 2007 > 1 > 2 > 85-87

Bacteria sense and respond to their environment, enabling adaptation to diverse niches, including multicellular eukaryotes. In this issue of Cell Host & Microbe, Torres et al. describe how the bacterium Staphylococcus aureus responds to heme as a molecular marker of the mammalian host environment. It is likely that mechanisms for sensing such markers evolved from systems that recognized cues present...

article

An Adaptive Immune Response in Drosophila?

Hervé Agaisse

Cell Host & Microbe > 2007 > 1 > 2 > 91-93

The ability to mount an adaptive immune response is thought to be an attribute restricted to vertebrates. A new study conducted in Drosophila demonstrates that invertebrate immunity can adapt to an immune challenge and mount a specific immune response.

article

The Stoichiometry of Antibody-Mediated Neutralization and Enhancement of West Nile Virus Infection

Theodore C. Pierson, Qing Xu, Steevenson Nelson, Theodore Oliphant, more

Cell Host & Microbe > 2007 > 1 > 2 > 135-145

Antibody binding to the icosahedral arrangement of envelope proteins on the surface of flaviviruses can result in neutralization or enhancement of infection. We evaluated how many antibodies must bind to a given epitope on West Nile virus (WNV) to achieve neutralization. The most potent monoclonal antibodies (mAbs) block infection at concentrations that result in low occupancy of accessible sites...

INFONA - science communication portal

Cell Host & Microbe

Viral Evasion of Autophagy

Rebuilding Host-Pathogen Interaction from the Ground Up: In Vitro Reconstitution of the Inflammasome

Salmonella SPI1 Effector SipA Persists after Entry and Cooperates with a SPI2 Effector to Regulate Phagosome Maturation and Intracellular Replication

A Two-Pronged Mechanism for HIV-1 Nef-Mediated Endocytosis of Immune Costimulatory Molecules CD80 and CD86

Bacterial Interference of Ubiquitination and Deubiquitination

HSV-1 ICP34.5 Confers Neurovirulence by Targeting the Beclin 1 Autophagy Protein

Host-Microbe Interactions: Fulfilling a Niche

ALIX Catches HIV

The Broad Antibacterial Activity of the Natural Antibody Repertoire Is Due to Polyreactive Antibodies

The Host-Microbe Interface: A New Voyage of Discovery

Type III Secretion Effectors of the IpaH Family Are E3 Ubiquitin Ligases

A Type III Secretion System in Vibrio cholerae Translocates a Formin/Spire Hybrid-like Actin Nucleator to Promote Intestinal Colonization

A Staphylococcus aureus Regulatory System that Responds to Host Heme and Modulates Virulence

A Plasmid-Based Reverse Genetics System for Animal Double-Stranded RNA Viruses

HIV-1 Nef Assembles a Src Family Kinase-ZAP-70/Syk-PI3K Cascade to Downregulate Cell-Surface MHC-I

A Reverse Genetics System for dsRNA Viruses

Antibodies to West Nile Virus: A Double-Edged Sword

Did Bacterial Sensing of Host Environments Evolve from Sensing within Microbial Communities?

An Adaptive Immune Response in Drosophila?

The Stoichiometry of Antibody-Mediated Neutralization and Enhancement of West Nile Virus Infection

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