scholarly journals Antiviral Effects of Curcumin on Adenovirus Replication

2020 ◽  
Vol 8 (10) ◽  
pp. 1524 ◽  
Author(s):  
Morgan R. Jennings ◽  
Robin J. Parks
Keyword(s):  
Gene Expression ◽  
Antimicrobial Agent ◽  
Human Adenovirus ◽  
Immunocompromised Patients ◽  
Severe Morbidity ◽  
Antiviral Effects ◽  
Replication Gene ◽  
Adenovirus Replication ◽  
Potential Therapeutics ◽  
Agent Treatment

Human adenovirus (HAdV) is a common pathogen that can cause severe morbidity and mortality in certain populations, including pediatric, geriatric, and immunocompromised patients. Unfortunately, there are no approved therapeutics to combat HAdV infections. Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different bacteria and viruses. In this study, we evaluated curcumin as an anti-HAdV agent. Treatment of cells in culture with curcumin reduced HAdV replication, gene expression, and virus yield, at concentrations of curcumin that had little effect on cell viability. Thus, curcumin represents a promising class of compounds for further study as potential therapeutics to combat HAdV infection.

scholarly journals Comparative Sequence Analysis of the Largest E1A Proteins of Human and Simian Adenoviruses

2002 ◽  
Vol 76 (16) ◽  
pp. 7968-7975 ◽  
Author(s):  
Nikita Avvakumov ◽  
Russ Wheeler ◽  
Jean Claude D'Halluin ◽  
Joe S. Mymryk
Keyword(s):  
Gene Expression ◽  
Human Adenovirus ◽  
Detailed Comparison ◽  
Adenovirus Type ◽  
Comparative Sequence Analysis ◽  
Regulatory Proteins ◽  
Carboxyl Terminus ◽  
Adenovirus E1a ◽  
Simian Adenovirus ◽  
Adenovirus Type 5

ABSTRACT The early region 1A (E1A) gene is the first gene expressed after infection with adenovirus and has been most extensively characterized in human adenovirus type 5 (hAd5). The E1A proteins interact with numerous cellular regulatory proteins, influencing a variety of transcriptional and cell cycle events. For this reason, these multifunctional proteins have been useful as tools for dissecting pathways regulating cell growth and gene expression. Despite the large number of studies using hAd5 E1A, relatively little is known about the function of the E1A proteins of other adenoviruses. In 1985, a comparison of E1A sequences from three human and one simian adenovirus identified three regions with higher overall levels of sequence conservation designated conserved regions (CR) 1, 2, and 3. As expected, these regions are critical for a variety of E1A functions. Since that time, the sequences of several other human and simian adenovirus E1A proteins have been determined. Using these, and two additional sequences that we determined, we report here a detailed comparison of the sequences of 15 E1A proteins representing each of the six hAd subgroups and several simian adenoviruses. These analyses refine the positioning of CR1, 2, and 3; define a fourth CR located near the carboxyl terminus of E1A; and suggest several new functions for E1A.

scholarly journals Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All

2016 ◽  
Vol 54 (6) ◽  
pp. 1479-1486 ◽  
Author(s):  
Eunkyung Song ◽  
Huanyu Wang ◽  
Doug Salamon ◽  
Preeti Jaggi ◽  
Amy Leber
Keyword(s):  
Respiratory Tract ◽  
Molecular Typing ◽  
Tertiary Care ◽  
Systemic Infection ◽  
Human Adenovirus ◽  
Healthy Children ◽  
Immunocompromised Patients ◽  
Pcr Assay ◽  
Low Levels ◽  
Respiratory Specimens

The FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention.

scholarly journals Adenovirus Late-Phase Infection Is Controlled by a Novel L4 Promoter

2010 ◽  
Vol 84 (14) ◽  
pp. 7096-7104 ◽  
Author(s):  
Susan J. Morris ◽  
Gillian E. Scott ◽  
Keith N. Leppard
Keyword(s):  
Gene Expression ◽  
Intermediate Phase ◽  
Expression Patterns ◽  
Late Phase ◽  
Adenovirus Vector ◽  
Human Adenovirus ◽  
Late Gene ◽  
Genome Replication ◽  
Late Gene Expression ◽  
Viral Genome Replication

ABSTRACT During human adenovirus 5 infection, a temporal cascade of gene expression leads ultimately to the production of large amounts of the proteins needed to construct progeny virions. However, the mechanism for the activation of the major late gene that encodes these viral structural proteins has not been well understood. We show here that two key positive regulators of the major late gene, L4-22K and L4-33K, previously thought to be expressed under the control of the major late promoter itself, initially are expressed from a novel promoter that is embedded within the major late gene and dedicated to their expression. This L4 promoter is required for late gene expression and is activated by a combination of viral protein activators produced during the infection, including E1A, E4 Orf3, and the intermediate-phase protein IVa2, and also by viral genome replication. This new understanding redraws the long-established view of how adenoviral gene expression patterns are controlled and offers new ways to manipulate that gene expression cascade for adenovirus vector applications.

scholarly journals The Adenovirus Dodecahedron: Beyond the Platonic Story

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 718
Author(s):  
Solène Besson ◽  
Charles Vragniau ◽  
Emilie Vassal-Stermann ◽  
Marie Claire Dagher ◽  
Pascal Fender
Keyword(s):  
Electron Microscopy ◽  
Viral Entry ◽  
Physiological Role ◽  
Human Adenovirus ◽  
Structural Determinants ◽  
Cryo Electron Microscopy ◽  
Therapeutic Development ◽  
Adenovirus Receptor ◽  
Adenovirus Replication ◽  
Potential Use

Many geometric forms are found in nature, some of them adhering to mathematical laws or amazing aesthetic rules. One of the best-known examples in microbiology is the icosahedral shape of certain viruses with 20 triangular facets and 12 edges. What is less known, however, is that a complementary object displaying 12 faces and 20 edges called a ‘dodecahedron’ can be produced in huge amounts during certain adenovirus replication cycles. The decahedron was first described more than 50 years ago in the human adenovirus (HAdV3) viral cycle. Later on, the expression of this recombinant scaffold, combined with improvements in cryo-electron microscopy, made it possible to decipher the structural determinants underlying their architecture. Recently, this particle, which mimics viral entry, was used to fish the long elusive adenovirus receptor, desmoglein-2, which serves as a cellular docking for some adenovirus serotypes. This breakthrough enabled the understanding of the physiological role played by the dodecahedral particles, showing that icosahedral and dodecahedral particles live more than a simple platonic story. All these points are developed in this review, and the potential use of the dodecahedron in therapeutic development is discussed.

scholarly journals Antiviral Activity of Resveratrol against Human and Animal Viruses

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yusuf Abba ◽  
Hasliza Hassim ◽  
Hazilawati Hamzah ◽  
Mohamed Mustapha Noordin
Keyword(s):  
Gene Expression ◽  
Viral Infections ◽  
Antioxidant Properties ◽  
Acid Synthesis ◽  
Antioxidant Effect ◽  
Viral Diseases ◽  
Polyphenolic Compound ◽  
Antiviral Effects

Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections bothin vitroandin vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβpathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.

scholarly journals Suppression of Adenovirus Replication by Cardiotonic Steroids

2016 ◽  
Vol 91 (3) ◽  
Author(s):  
Filomena Grosso ◽  
Peter Stoilov ◽  
Clifford Lingwood ◽  
Martha Brown ◽  
Alan Cochrane
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
Rna Splicing ◽  
Antiviral Effect ◽  
Early Gene ◽  
Genome Replication ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Human Adenoviruses ◽  
Adenovirus Replication

ABSTRACT The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses revealed that both drugs altered E1A RNA splicing (favoring the production of 13S over 12S RNA) early in infection and partially blocked the transition from 12S and 13S to 9S RNA at late stages of virus replication. Expression of multiple late viral protein mRNAs was lost in the presence of either drug, consistent with the observed block in viral DNA replication. The antiviral effect was dependent on the continued presence of the drug and was rapidly reversible. RIDK34, a derivative of convallotoxin, although having more potent antiviral activity, did not show an improved selectivity index. All three drugs reduced metabolic activity to some degree without evidence of cell death. By blocking adenovirus replication at one or more steps beyond the onset of E1A expression and prior to genome replication, digoxin and digitoxin show potential as antiviral agents for treatment of serious adenovirus infections. Furthermore, understanding the mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will guide the development of novel antiviral therapies. IMPORTANCE Despite human adenoviruses being a common and, in some instances, life-threating pathogen in humans, there are few well-tolerated therapies. In this report, we demonstrate that two cardiotonic steroids already in use in humans, digoxin and digitoxin, are potent inhibitors of multiple adenovirus species. A synthetic derivative of the cardiotonic steroid convallotoxin was even more potent than digoxin and digitoxin when tested with HAdV-C5. These drugs alter the cascade of adenovirus gene expression, acting after initiation of early gene expression to block viral DNA replication and synthesis of viral structural proteins. These findings validate a novel approach to treating adenovirus infections through the modulation of host cell processes.

Human adenovirus replication in immunocompetent Syrian hamsters can be attenuated with chlorpromazine or cidofovir

2010 ◽  
Vol 12 (5) ◽  
pp. 435-445 ◽  
Author(s):  
Iulia Diaconu ◽  
Vincenzo Cerullo ◽  
Sophie Escutenaire ◽  
Anna Kanerva ◽  
Gerd J. Bauerschmitz ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
Syrian Hamsters ◽  
Adenovirus Replication

scholarly journals Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

Viruses ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 1409-1428 ◽  
Author(s):  
Karoly Toth ◽  
Baoling Ying ◽  
Ann Tollefson ◽  
Jacqueline Spencer ◽  
Lata Balakrishnan ◽  
...  
Keyword(s):  
Human Adenovirus ◽  
Syrian Hamsters ◽  
Adenovirus Replication

scholarly journals Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Suppresses Human Adenovirus Gene Expression and Replication

2019 ◽  
Vol 93 (12) ◽  
Author(s):  
Bratati Saha ◽  
Robin J. Parks
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Hdac Inhibitor ◽  
Trichostatin A ◽  
Human Adenovirus ◽  
Class I ◽  
Virus Yield ◽  
Hdac Activity ◽  
Viral Genes ◽  
Efficient Expression

ABSTRACTHuman adenovirus (HAdV) causes minor illnesses in most patients but can lead to severe disease and death in pediatric, geriatric, and immunocompromised individuals. No approved antiviral therapy currently exists for the treatment of these severe HAdV-induced diseases. In this study, we show that the pan-histone deacetylase (HDAC) inhibitor SAHA reduces HAdV-5 gene expression and DNA replication in tissue culture, ultimately decreasing virus yield from infected cells. Importantly, SAHA also reduced gene expression from more virulent and clinically relevant serotypes, including HAdV-4 and HAdV-7. In addition to SAHA, several other HDAC inhibitors (e.g., trichostatin A, apicidin, and panobinostat) also affected HAdV gene expression. We determined that loss of class I HDAC activity, mainly HDAC2, impairs efficient expression of viral genes, and that E1A physically interacts with HDAC2. Our results suggest that HDAC activity is necessary for HAdV replication, which may represent a novel pharmacological target in HAdV-induced disease.IMPORTANCEAlthough human adenovirus (HAdV) can cause severe diseases that can be fatal in some populations, there are no effective treatments to combat HAdV infection. In this study, we determined that the pan-histone deacetylase (HDAC) inhibitor SAHA has inhibitory activity against several clinically relevant serotypes of HAdV. This U.S. Food and Drug Administration-approved compound affects various stages of the virus lifecycle and reduces virus yield even at low concentrations. We further report that class I HDAC activity, particularly HDAC2, is required for efficient expression of viral genes during lytic infection. Investigation of the mechanism underlying SAHA-mediated suppression of HAdV gene expression and replication will enhance current knowledge of virus-cell interaction and may aid in the development of more effective antivirals with lower toxicity for the treatment of HAdV infections.

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