Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy

Crenshaw, Brennetta J.; Jones, Leandra B.; Bell, Courtnee’ R.; Kumar, Sanjay; Matthews, Qiana L.

doi:10.3390/biomedicines7030061

Cited by 70 publications

(71 citation statements)

References 168 publications

(222 reference statements)

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“…HAdVs outbreaks have been documented for healthy adults in closed or crowded settings, such as military training site [ 9 ]. HAdV3, HAdV4, HAdV7, HAdV8, HAdV14, and HAdV55 are commonly linked to outbreaks, more virulent and likely to spread [ 10 ]. Among them, HAdV serotype 7 (HAdV7) seems to be the most virulent, causing severe complications and significant mortality.…”

Section: Introductionmentioning

confidence: 99%

Binding Mechanism Elucidation of the Acute Respiratory Disease Causing Agent Adenovirus of Serotype 7 to Desmoglein-2

Hograindleur

Effantin

Fenel

et al. 2020

Viruses

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The study of viruses causing acute respiratory distress syndromes (ARDS) is more essential than ever at a time when a virus can create a global pandemic in a matter of weeks. Among human adenoviruses, adenovirus of serotype 7 (HAdV7) is one of the most virulent serotypes. This virus regularly re-emerges in Asia and has just been the cause of several deaths in the United States. A critical step of the virus life cycle is the attachment of the knob domain of the fiber (HAd7K) to the cellular receptor desmoglein-2 (DSG2). Complexes between the fiber knob and two extracellular domains of DSG2 have been produced. Their characterization by biochemical and biophysical methods show that these two domains are sufficient for the interaction and that the trimeric HAd7K could accommodate up to three DSG2 receptor molecules. The cryo-electron microscopy (cryo-EM) structure of these complexes at 3.1 Å resolution confirmed the biochemical data, and allowed the identification of the critical amino acid residues for this interaction, which shows similarities with other DSG2 interacting adenoviruses, despite a low homology in the primary sequences.

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Section: Introductionmentioning

confidence: 99%

Binding Mechanism Elucidation of the Acute Respiratory Disease Causing Agent Adenovirus of Serotype 7 to Desmoglein-2

Hograindleur

Effantin

Fenel

et al. 2020

Viruses

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“…ABs, whose size varies between 1 and 5 µm, are released by apoptotic cells as blebs [20][21][22]. AB secretion serves as a signal stimulating phagocytosis of apoptotic cells before the induction of secondary necrosis [21,23]. Due to the small differences in physical properties and composition, discrimination between extracellular vesicle (EV) populations remains difficult.…”

Section: Introductionmentioning

confidence: 99%

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

et al. 2019

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Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease.

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“…HAdV can lead to severe disease in seemingly healthy individuals, with no obvious susceptibility factors that impact disease manifestation ( Bhatti and Dhamoon, 2017 ; Binder et al, 2017 ; Kojaoghlanian et al, 2003 ; Lion, 2014 ). A recent outbreak that gained much attention in the popular press involved HAdV-7 at the Wanaque Center for Nursing and Rehabilitation in New Jersey, infecting ∼35 people, including 23 children, and resulting in 11 deaths within the pediatric population ( Crenshaw et al, 2019 ). There are no approved anti-HAdV therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Identification of human adenovirus replication inhibitors from a library of small molecules targeting cellular epigenetic regulators

Saha

Parks

2021

Virology

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Human adenovirus (HAdV) can cause severe disease in certain at-risk populations such as newborns, the elderly and those with compromised immune systems. Unfortunately, no FDA-approved anti-HAdV drug is currently available for treatment. Within the nucleus of infected cells, the HAdV genome associates with histones and forms a chromatin-like structure during early infection, and viral gene expression appears regulated by cellular epigenetic processes. Thus, one potential therapeutic strategy to combat HAdV disease may be to target the cellular proteins involved in modifying the viral nucleoprotein structure and facilitating HAdV gene expression and replication. We have screened a panel of small molecules that modulate the activity of epigenetic regulatory proteins for compounds affecting HAdV gene expression. Several of the compounds, specifically chaetocin, gemcitabine and lestaurtinib, reduced HAdV recovery by 100- to 1000-fold, while showing limited effect on cell health, suggesting that these compounds may indeed be promising as anti-HAdV therapeutics.

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Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy

Cited by 70 publications

References 168 publications

Binding Mechanism Elucidation of the Acute Respiratory Disease Causing Agent Adenovirus of Serotype 7 to Desmoglein-2

Binding Mechanism Elucidation of the Acute Respiratory Disease Causing Agent Adenovirus of Serotype 7 to Desmoglein-2

Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles

Identification of human adenovirus replication inhibitors from a library of small molecules targeting cellular epigenetic regulators

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