Outbreak of Pneumonia Associated with Emergent Human Adenovirus Serotype 14—Southeast Alaska, 2008

Esposito, Douglas H.; Gardner, Tracie J.; Schneider, Eileen; Stockman, Lauren J.; Tate, Jacqueline E.; Panozzo, Catherine A.; Robbins, Cheryl L.; Jenkerson, Sue Anne; Thomas, Lorita; Watson, Colleen M.; Curns, Aaron T.; Erdman, Dean D.; Lu, Xiaoyan; Cromeans, Theresa L.; Westcott, M.; Humphries, Catherine; Ballantyne, Jayme; Fischer, Gayle E.; McLaughlin, Joseph; Armstrong, Gregory L.; Anderson, Larry J.

doi:10.1086/653498

Cited by 44 publications

(33 citation statements)

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“…Nevertheless, of concern in the cohort described here is the third death, which occurred in a previously well patient. The immunocompetent woman was a smoker, and smoking has been identified as an independent risk factor possibly facilitating transmission of HAdV-14p1 ( 11 ). However, the low rate of infections (5%) observed by Esposito et al ( 11 ) in household contacts of persons infected with the emerging virus suggests that infection is unlikely to spread in the community.…”

Section: Discussionmentioning

confidence: 99%

“…The immunocompetent woman was a smoker, and smoking has been identified as an independent risk factor possibly facilitating transmission of HAdV-14p1 ( 11 ). However, the low rate of infections (5%) observed by Esposito et al ( 11 ) in household contacts of persons infected with the emerging virus suggests that infection is unlikely to spread in the community. Efficient transmission of HAdV-14p1 appears to require close physical contact, as supported by the observation that in barracked communities used for military trainees in the United States, antibody titers demonstrated recent exposure after entry to the facility ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

“…The 252glu site is conserved in all other species B HAdVs and is located in the F–G loop of the fiber protein knob near a putative host receptor binding site. Further sequencing of the hexon gene hypervariable regions 1–7 and the E1A genes demonstrated that this emerging HAdV-14 was clearly separable from the reference strain de Wit (genome restriction type HAdV-14p) ( 9 , 11 ). This new genomic variant has been designated HAdV-14p1 on the basis of novel restriction profiles.…”

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confidence: 95%

“…Overall, 38% of patients were hospitalized, 17% were admitted to intensive care units, and 5% died. During September 2008, an outbreak was reported with 32 cases of pneumonia on Prince of Wales Island off the coast of Alaska ( 11 ). In the United States, the earliest documented case of HAdV-14 infection, by retrospective testing, occurred in California during December 2003, and the most recent evidence of HAdV-14 had been in Pennsylvania during June 2009 ( 7 ).…”

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confidence: 99%

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Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010

Carr¹,

Kajon²,

Lu³

et al. 2011

Emerg. Infect. Dis.

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Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009–July 31, 2010, and describe 9 cases of HAdV-14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

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Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010

Carr¹,

Kajon²,

Lu³

et al. 2011

Emerg. Infect. Dis.

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“…Thirty-eight percent of these patients were hospitalized, including 17% who were admitted to intensive care units; 5% of patients died. Outbreaks of Ad14P1 infection were subsequently detected in other five bases and in civilian populations in Washington (19), Oregon (20), Alaska (21), Wisconsin, and Pennsylvania (22,23), as well as in Canada (24), China (25), and South Korea (26). At this point, the molecular basis for the high pathogenicity and/or virulence of Ad14P1 is unclear.…”

mentioning

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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Adenoviruses

Heim,

Kajon

2023

ClinMicroNow

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In 1953, Rowe and colleagues described an “adenoid degeneration agent” that induced spontaneous deterioration of tissue cultures prepared from adenoids of children. In the mid1960s, human adenoviruses (HAdV) were found to cause tumors in rodents, prompting studies that revealed fundamental processes of molecular biology but failed to link the virus convincingly to human cancer. HAdV belong to the Adenoviridae family, Mastadenovirus genus. Adenoviruses are large, nonenveloped, icosahedral viruses 70 to 90 nm in diameter. Adenovirus infections can be epidemic, endemic, or sporadic, with the pattern of circulation, specific syndrome, and severity varying by type, population, and route of exposure. Adenovirus‐associated gastroenteritis is caused primarily by types 40 and 41 of species HAdV‐F, which are also known as the “enteric adenoviruses.”

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Outbreak of Pneumonia Associated with Emergent Human Adenovirus Serotype 14—Southeast Alaska, 2008

Cited by 44 publications

References 13 publications

Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010

Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010

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

Adenoviruses

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