Genome sequences of Human Adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America

Houng, Huo-Shu H.; Gong, Heping; Kajon, Adriana E.; Jones, Mary Smith McCrory; Kuschner, Robert A.; Lyons, Arthur; Lott, Lisa; Lin, Kuei-Hsiang; Metzgar, David

doi:10.1186/1465-9921-11-116

Cited by 40 publications

(53 citation statements)

References 33 publications

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“…2). Sequences of the E1B 20K genes from Ad14p1 isolates 1986T and 22039 were 100% identical to the published sequence of Ad14p1 (GenBank accession number FJ822614), which is in agreement with the work of Houng et al (2). Therefore, the observed lp and cyt traits observed in the Ad14p1 isolates could not be explained by a mutation that alters the function of the E1B 20K protein in cells infected with the Ad14p1 isolates.…”

Section: Ad14p1 Isolates Exhibit Large-plaque and Cytocidal Phenotypessupporting

confidence: 78%

“…Naval Health Research Center. For initial studies, we used Ad14p1 isolate 1986T from a fatal infection at Lackland Air Force Base in Texas and Ad14p1 isolate NHRC22039 from an outbreak at the Marine Corps Recruit Depot in California (2,11). The isolates were propagated, and titers were determined by plaque assay in A549 cells.…”

Section: Ad14p1 Isolates Exhibit Large-plaque and Cytocidal Phenotypesmentioning

confidence: 99%

“…The emergent Ad14 strain (Ad14p1) was isolated from military personnel at geographically distinct locations. Sequencing of the isolates determined that the strains were 100% identical in the coding regions and differed by just 0.3% from the prototype Ad14 deWit strain (2). Currently, Ad14p1 is circulating worldwide and has been identified as the causative agent in numerous cases of acute respiratory distress syndrome (ARDS); these strains are also highly homologous to the military isolates (3)(4)(5)(6).…”

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confidence: 99%

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Low-Level Expression of the E1B 20-Kilodalton Protein by Adenovirus 14p1 Enhances Viral Immunopathogenesis

Radke

Yong

Cook

2016

J Virol

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Adenovirus 14p1 (Ad14p1) is an emergent variant of Ad serotype 14 (Ad14) that has caused increased severity of respiratory illnesses during globally distributed outbreaks, including cases of acute respiratory distress syndrome and death. We found that human cell infection with Ad14p1 results in markedly decreased expression of the E1B 20-kilodalton (20K) protein compared to that with infection with wild-type (wt) Ad14. This reduced Ad14p1 E1B 20K expression caused a loss-of-function phenotype of Ad-infected cell corpses that, in contrast to cells infected with wt Ad14, either failed to repress or increased NF-B-dependent, proinflammatory cytokine responses of responder human alveolar macrophages. A small-animal model of Ad14-induced lung infection was used to test the translational relevance of these in vitro observations. Intratracheal infection of Syrian hamsters with Ad14p1 caused a marked, patchy bronchopneumonia, whereas hamster infection with wt Ad14 caused minimal peribronchial inflammation. These results suggest that this difference in E1B 20K gene expression during Ad14p1 infection and its modulating effect on the interactions between Ad14-infected cells and the host innate immune response could explain the increased immunopathogenic potential and associated increase in clinical illness in some people infected with the Ad14p1 outbreak strain. IMPORTANCE We previously reported that Ad-infected human cells exhibit E1B 19K-dependent repression of virally induced, NF-B-depen-

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Section: Ad14p1 Isolates Exhibit Large-plaque and Cytocidal Phenotypessupporting

confidence: 78%

Section: Ad14p1 Isolates Exhibit Large-plaque and Cytocidal Phenotypesmentioning

confidence: 99%

mentioning

confidence: 99%

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Low-Level Expression of the E1B 20-Kilodalton Protein by Adenovirus 14p1 Enhances Viral Immunopathogenesis

Radke

Yong

Cook

2016

J Virol

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“…Our data showing greater spread and oncolytic activity of Ad14P1 than of Ad14 in a human epithelial cancer model pointed toward better infectivity and/or replication of Ad14P1. The genomes of the two viruses differ by an insertion in E1A and a small deletion in the fiber knob (48). We tested the hypothesis that the mutation in the fiber knob would account for the observed differences.…”

Section: Discussionmentioning

confidence: 99%

“…7B). The genomes of the two viruses differ by an insertion in the E1A gene and a small deletion in the fiber knob gene (48). In this study, we tested the hypothesis that the more efficient Ad14P1 production in xenograft tumors and, potentially, its higher pathogenicity are linked to the mutation within the Ad14P1 fiber knob.…”

Section: Shedding Of the Dsg2 Extracellular Domain Triggered By Ad3mentioning

confidence: 99%

Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses Ad3, Ad14, and Ad14P1

Wang

Ducournau

Saydaminova

et al. 2015

J Virol

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We recently discovered that desmoglein 2 (DSG2) is a receptor for human adenovirus species B serotypes Ad3, Ad7, Ad11, and Ad14. Ad3 is considered to be a widely distributed human pathogen. Ad3 binding to DSG2 triggers the transient opening of epithelial junctions. Here, we further delineate the mechanism that leads to DSG2-mediated epithelial junction opening in cells exposed to Ad3 and recombinant Ad3 fiber proteins. We identified an Ad3 fiber knob-dependent pathway that involves the phosphorylation of mitogen-activated protein (MAP) kinases triggering the activation of the matrix-metalloproteinase ADAM17. ADAM17, in turn, cleaves the extracellular domain of DSG2 that links epithelial cells together. The shed DSG2 domain can be detected in cell culture supernatant and also in serum of mice with established human xenograft tumors. We then extended our studies to Ad14 and Ad14P1. Ad14 is an important research and clinical object because of the recent appearance of a new, more pathogenic strain (Ad14P1). In a human epithelial cancer xenograft model, Ad14P1 showed more efficient viral spread and oncolysis than Ad14. Here, we tested the hypothesis that a mutation in the Ad14P1 fiber knob could account for the differences between the two strains. While our X-ray crystallography studies suggested an altered three-dimensional (3D) structure of the Ad14P1 fiber knob in the F-G loop region, this did not significantly change the fiber knob affinity to DSG2 or the intracellular signaling and DSG2 shedding in epithelial cancer cells. IMPORTANCE A number of widely distributed adenoviruses use the epithelial junction protein DSG2 as a receptor for infection and lateral spread. Interaction with DSG2 allows the virus not only to enter cells but also to open epithelial junctions which form a physicalbarrier to virus spread. Our study elucidates the mechanism beyond virus-triggered junction opening with a focus on adenovirus serotype 3. Ad3 binds to DSG2 with its fiber knob domain and triggers intracellular signaling that culminates in the cleavage of the extracellular domain of DSG2, thereby disrupting DSG2 homodimers between epithelial cells. We confirmed this pathway with a second DSG2-interacting serotype, Ad14, and its recently emerged strain Ad14P1. These new insights in basic adenovirus biology can be employed to develop novel drugs to treat adenovirus infection as well as be used as tools for gene delivery into epithelial tissues or epithelial tumors. W e recently discovered that desmoglein 2 (DSG2) is a receptor for human adenovirus species B serotypes Ad3, Ad7, Ad11, and Ad14 (1-3). DSG2 is a calcium-binding transmembrane glycoprotein belonging to the cadherin protein family. In epithelial cells of the respiratory, gastrointestinal, and urinary tracts, DSG2 is a component of the cell-cell adhesion structure (4). It is well established that in addition to maintaining cell adhesion, DSG2 is also involved in intracellular signaling (5). Its cytoplasmic tail interacts with a series of proteins, including plakoglobi...

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Isolation and molecular characterization of Adenovirus in suspected acute flaccid paralysis patients: A preliminary report from Pakistan

Khattak

Shah

Zaidi³

et al. 2022

Arch Virol

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Genome sequences of Human Adenovirus 14 isolates from mild respiratory cases and a fatal pneumonia, isolated during 2006-2007 epidemics in North America

Cited by 40 publications

References 33 publications

Low-Level Expression of the E1B 20-Kilodalton Protein by Adenovirus 14p1 Enhances Viral Immunopathogenesis

Low-Level Expression of the E1B 20-Kilodalton Protein by Adenovirus 14p1 Enhances Viral Immunopathogenesis

Intracellular Signaling and Desmoglein 2 Shedding Triggered by Human Adenoviruses Ad3, Ad14, and Ad14P1

Isolation and molecular characterization of Adenovirus in suspected acute flaccid paralysis patients: A preliminary report from Pakistan

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