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Veterinary Ophthalmology May 2023We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)-2 vaccinations and assessed the utility of CAV-1 and CAV-2...
OBJECTIVE
We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)-2 vaccinations and assessed the utility of CAV-1 and CAV-2 titers in elucidation of its etiopathogenesis.
ANIMALS STUDIED
Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs.
PROCEDURES
The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age-matched dogs without corneal edema but with CAV titers were included as controls.
RESULTS
Mean CAV-1 and CAV-2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV-1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11-fold increase) suggesting infection with wild-type CAV-1. The six other cases did not appear to be associated with CAV infection or vaccination.
CONCLUSION
Keratouveitis continues to occur despite the advent of CAV-2 vaccinations. While this study found no evidence to indicate CAV-2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild-type CAV-1 infection is a possible cause.
Topics: Dogs; Animals; Dog Diseases; Corneal Edema; Adenoviruses, Canine; Vaccination; Keratitis; Adenoviridae Infections
PubMed: 36999558
DOI: 10.1111/vop.13085 -
The Veterinary Quarterly Dec 2017Haemorrhagic enteritis virus (HEV), an adenovirus associated with acute haemorrhagic gastro-intestinal disease of 6-11-week old turkeys predominantly hampers both... (Review)
Review
Haemorrhagic enteritis virus (HEV), an adenovirus associated with acute haemorrhagic gastro-intestinal disease of 6-11-week old turkeys predominantly hampers both humoral and cellular immunity. Affected birds are more prone to secondary complications (e.g. colibacillosis and clostridiosis) and failure to mount an effective vaccine-induced immune response. HEV belongs to the new genus Siadenovirus. Feco-oral transmission is the main route of entry of the virus and it mainly colonizes bursa, intestine and spleen. Both naturally occurring virulent and avirulent strains of HEVs are serologically indistinguishable. Recent findings revealed that ORF1, E3 and fib genes are the key factors affecting virulence. The adoption of suitable diagnostic tools, proper vaccination and biosecurity measures have restrained the occurrence of disease epidemics. For diagnostic purposes, the best source of HEV is either intestinal contents or samples from spleen. For rapid detection highly sensitive and specific tests such as quantitative real-time PCR based on Taq man probe has been designed. Avirulent strains of HEV or MSDV can be effectively used as live vaccines. Novel vaccines include recombinant hexon protein-based subunit vaccines or recombinant virus-vectored vaccines using fowl poxvirus (FPV) expressing the native hexon of HEV. Notably, subunit vaccines and recombinant virus vectored vaccines altogether offer high protection against challenge or field viruses. Herein, we converse a comprehensive analysis of the HEV genetics, disease pathobiology, advancements in diagnosis and vaccination along with appropriate prevention and control strategies.
Topics: Adenoviridae Infections; Animals; Enteritis; Poultry Diseases; Siadenovirus; Turkeys; Vaccination; Viral Vaccines
PubMed: 28024457
DOI: 10.1080/01652176.2016.1277281 -
Antiviral Research Nov 2018The repurposing of drugs approved by the regulatory agencies for other indications is emerging as a valuable alternative for the development of new antimicrobial...
The repurposing of drugs approved by the regulatory agencies for other indications is emerging as a valuable alternative for the development of new antimicrobial therapies, involving lower risks and costs than the de novo development of novel antimicrobial drugs. Adenovirus infections have showed a steady increment in recent years, with a high clinical impact in both immunosuppressed and immunocompetent patients. In this context, the lack of a specific drug to treat these infections supports the search for new therapeutic alternatives. In this study, we examined the anti-HAdV properties of mifepristone, a commercially available synthetic steroid drug. Mifepristone showed significant in vitro anti-HAdV activity at low micromolar concentrations with little cytotoxicity. Our mechanistic assays suggest that this drug could affect the microtubule transport, interfering with the entry of the virus into the nucleus and therefore inhibiting HAdV infection.
Topics: A549 Cells; Adenoviridae Infections; Adenoviruses, Human; Animals; Antiviral Agents; Drug Repositioning; Female; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; Mifepristone
PubMed: 30268911
DOI: 10.1016/j.antiviral.2018.09.011 -
Scientific Reports Aug 2018Adenovirus-based vectors are among the most commonly used platforms for gene delivery and gene therapy studies. One of the obstacles for potential application is...
Adenovirus-based vectors are among the most commonly used platforms for gene delivery and gene therapy studies. One of the obstacles for potential application is dose-related toxicity. We show here that adenovirus infection and Ad-mediated gene delivery can be enhanced by inhibitors of bromodomain and extra-terminal (BET) family proteins. We showed that JQ1, but not its inactive enantiomer (-)-JQ1, dose-dependently promoted Ad infection and Ad-mediated gene delivery in both epithelial and lymphocyte cells. Given orally, JQ1 also enhanced transgene expression in a murine tumor model. Inhibitors of histone deacetylases (HDACi) are among the commonly reported small molecule compounds which enhance Ad-mediated gene delivery. We found that JQ1 treatment did not cause histone acetylation nor expression of Ad attachment receptor CAR. Instead, JQ1 treatment induced an increase in BRD4 association with CDK9, a subunit of P-TEFb of transcription elongation. Concurrently, we showed that CDK9 inhibition blocked Ad infection and JQ1 enhancement on the infection. The study exemplifies the potentials of BET inhibitors like JQ1 in oncolytic virotherapy.
Topics: Adenoviridae; Adenoviridae Infections; Administration, Oral; Animals; Azepines; Cyclin-Dependent Kinase 9; Disease Models, Animal; Enzyme Inhibitors; Epithelial Cells; Gene Transfer Techniques; Genetic Vectors; Lymphocytes; Mice; Nuclear Proteins; Protein Binding; Transcription Factors; Transformation, Genetic; Triazoles
PubMed: 30068949
DOI: 10.1038/s41598-018-28421-x -
American Journal of Respiratory and... Apr 2019
Topics: Adenoviridae Infections; Disease Outbreaks; Humans; United States
PubMed: 30932693
DOI: 10.1164/rccm.1997P13 -
BMC Pediatrics Jan 2023The purpose of this study was to investigate the typing of adenovirus (AdV) infection in children hospitalized with acute respiratory tract infection (ARTI) and its...
BACKGROUND
The purpose of this study was to investigate the typing of adenovirus (AdV) infection in children hospitalized with acute respiratory tract infection (ARTI) and its clinical characteristics.
METHODS
Samples from 7832 hospitalized children with ARTIs from January 2021 to June 2022 were tested by multiplex PCR for AdV. AdV hex neighborhood genes were amplified and sequenced for typing by nested PCR.
RESULTS
Three hundred twenty-eight cases were positive for AdV with rate of 4.48% (328/7832). No statistical difference in the rate of AdV detection was observed in different ages (P > 0.05). Among the 328 cases, 305 cases underwent amplification and sequence determination of AdV five-neighborhood, six-neighborhood and fibronectin genes. Only 237 cases were sequenced successfully for all 3 genetic fragments. The typing results of 231 cases with 3 genes were consistent, with 49.78% (115/231) of type 3, 41.56% (96/231) of type 7 and 8.66% (20/231) of other types identified. The main clinical symptoms in 231 children hospitalized with ARTI who were AdV positive were cough, sputum not easily coughable, Wheezing or shortness of breath and fever. Clinical diagnoses of 231 cases included: acute bronchitis 3.03% (7/231), capillary bronchitis 16.45% (38/231), pneumonia (mild/severe) 76.62% (177/231) (68.40% (158/231) in mild and 8.23% (19/231) in severe cases), bronchial asthma combined with pulmonary infection 3.46% (8/231). Higher percentage of shortness of breath, multilobar infiltration, and pleural effusion were found in type 7. Calcitoninogen in type 7 were significantly higher than those of type 3 and other types, and the white blood cell count was lower than those of type 3 and other types, and the difference was statistically significant (P < 0.05).
CONCLUSION
AdV type 3 and 7 were frequently found in hospitalized children with acute lower respiratory tract involvement. AdV type 7 seems to be associated with more severe outcome.
Topics: Child; Humans; Infant; Adenoviridae; Adenoviridae Infections; Bronchitis; Dyspnea; Multiplex Polymerase Chain Reaction; Pneumonia; Respiratory Tract Infections; Child, Preschool
PubMed: 36647010
DOI: 10.1186/s12887-023-03840-6 -
European Journal of Medical Research Mar 2023Adenoviral-mediated keratoconjunctivitis is among the emergency diseases of ophthalmology with long-term sequels. The role of adenovirus infection, ocular-related...
PURPOSE
Adenoviral-mediated keratoconjunctivitis is among the emergency diseases of ophthalmology with long-term sequels. The role of adenovirus infection, ocular-related genotypes, and association with ocular symptoms need to be investigated for epidemiological as well as clinical purposes.
METHODS
The affected patients from two close keratoconjunctivitis epidemics were included in the study. The swab samples were taken from patients; the total DNA was extracted and then used as a template for in-house Real-time PCR. Besides, partial Hexon genes of 11 adenovirus positive samples were amplified and submitted to sanger sequencing. Moreover, they were finally evaluated by phylogenetic analysis.
RESULTS
Of 153 patients, 92 (60.1%) were males and 47 cases (30.7%) had a history of eye infection in the family or colleagues. Real-time PCR tests of 126 samples (82.4%) were positive for adenovirus, and all eleven cases that underwent sequencing analysis were determined to be group 8 (HAdV-D8). Adenovirus infection has a significant relationship with infection among family or colleagues (p = 0.048), membrane formation (p = 0.047), conjunctival bleeding (p = 0.046), tearing, and pain(p < 0.05).
CONCLUSIONS
The results indicated that Adenovirus is the major cause of keratoconjunctivitis, and HAdV-D8 was the most common genotype in the area. There were some clinical manifestations associated with Adenovirus infection of the conjunctiva.
Topics: Male; Humans; Female; Molecular Epidemiology; Iran; Genotype; Phylogeny; Keratoconjunctivitis; Adenoviridae Infections
PubMed: 36859343
DOI: 10.1186/s40001-022-00928-0 -
Journal of Virology Jul 2019Here, we show that the cellular DNA replication protein and ATR substrate SMARCAL1 is recruited to viral replication centers early during adenovirus infection and is...
Here, we show that the cellular DNA replication protein and ATR substrate SMARCAL1 is recruited to viral replication centers early during adenovirus infection and is then targeted in an E1B-55K/E4orf6- and cullin RING ligase-dependent manner for proteasomal degradation. In this regard, we have determined that SMARCAL1 is phosphorylated at S123, S129, and S173 early during infection in an ATR- and CDK-dependent manner, and that pharmacological inhibition of ATR and CDK activities attenuates SMARCAL1 degradation. SMARCAL1 recruitment to viral replication centers was shown to be largely dependent upon SMARCAL1 association with the RPA complex, while Ad-induced SMARCAL1 phosphorylation also contributed to SMARCAL1 recruitment to viral replication centers, albeit to a limited extent. SMARCAL1 was found associated with E1B-55K in adenovirus E1-transformed cells. Consistent with its ability to target SMARCAL1, we determined that E1B-55K modulates cellular DNA replication. As such, E1B-55K expression initially enhances cellular DNA replication fork speed but ultimately leads to increased replication fork stalling and the attenuation of cellular DNA replication. Therefore, we propose that adenovirus targets SMARCAL1 for degradation during infection to inhibit cellular DNA replication and promote viral replication. Viruses have evolved to inhibit cellular DNA damage response pathways that possess antiviral activities and utilize DNA damage response pathways that possess proviral activities. Adenovirus has evolved, primarily, to inhibit DNA damage response pathways by engaging with the ubiquitin-proteasome system and promoting the degradation of key cellular proteins. Adenovirus differentially regulates ATR DNA damage response signaling pathways during infection. The cellular adenovirus E1B-55K binding protein E1B-AP5 participates in ATR signaling pathways activated during infection, while adenovirus 12 E4orf6 negates Chk1 activation by promoting the proteasome-dependent degradation of the ATR activator TOPBP1. The studies detailed here indicate that adenovirus utilizes ATR kinase and CDKs during infection to promote the degradation of SMARCAL1 to attenuate normal cellular DNA replication. These studies further our understanding of the relationship between adenovirus and DNA damage and cell cycle signaling pathways during infection and establish new roles for E1B-55K in the modulation of cellular DNA replication.
Topics: A549 Cells; Adenoviridae Infections; Adenovirus E1B Proteins; Adenoviruses, Human; Ataxia Telangiectasia Mutated Proteins; Cyclin-Dependent Kinases; DNA Damage; DNA Helicases; DNA Replication; DNA-Binding Proteins; Humans; Nuclear Proteins; Phosphorylation; Proteasome Endopeptidase Complex; Signal Transduction; Ubiquitin; Virus Replication
PubMed: 30996091
DOI: 10.1128/JVI.00402-19 -
The American Journal of Case Reports Aug 2022BACKGROUND Human adenovirus is a well-known pathogen that can potentially lead to severe infection in immunocompromised patients. Adenovirus infections in solid-organ...
BACKGROUND Human adenovirus is a well-known pathogen that can potentially lead to severe infection in immunocompromised patients. Adenovirus infections in solid-organ transplant recipients can range from asymptomatic to severe, prolonged, disseminated disease, and have a significant impact on morbidity, mortality, and graft survival. The clinical manifestations vary from asymptomatic and flu-like illness to severe life-threatening viremia with multi-organ failure. Post-transplant adenovirus infection is well described in kidney recipients, but in adult liver transplant recipients the impact of the virus is not well described. In this report, a case of disseminated adenovirus infection with subsequent fatal acute liver failure in a post-kidney transplant patient is presented. CASE REPORT A 51-year-old man underwent a deceased kidney transplantation for focal segmental glomerulosclerosis. Shortly after the kidney transplantation, he received multiple plasmapheresis with additional steroid treatments for cellular rejection and reoccurrence of his primary kidney disease. Three weeks after the kidney transplant, he developed a disseminated adenovirus infection with subsequent acute liver failure. Despite the early diagnosis and aggressive treatment, the patient died. CONCLUSIONS Patients with organ transplantation with autoimmune background etiology are usually over-immunosuppressed to avoid early rejection. In this population, opportunistic infections are not rare. Fever, general malaise, and transplant organ dysfunction are the first signs of bacterial or viral infection. Early infectious diseases work-up, including tissue biopsy, is fundamental to establish a diagnosis. Broad antibiotic and possible antiviral aggressive treatment are mandatory.
Topics: Adenoviridae; Adenoviridae Infections; Adult; Humans; Kidney; Kidney Transplantation; Liver Failure, Acute; Male; Middle Aged; Postoperative Complications
PubMed: 35932113
DOI: 10.12659/AJCR.936564 -
International Journal of Nanomedicine 2023Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The...
PURPOSE
Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The results support in vitro adenovirus studies, including isolation and culture, pathogenesis research, and antiviral drug screening.
METHODS
HSAEC1-KT, HuLEC-5a and HELF cells were cocultured in RADA16-I hydrogel scaffolds to construct an airway organoid model. Adenovirus was used to infect this model for adenovirus-related studies. The morphological characteristics and the proliferation and activity of airway organoids before and after adenovirus infection were evaluated. The expression of the airway organoid marker proteins CC10, KRT8, AQP5, SPC, VIM and CD31 was detected. TEM and qPCR were used to detect adenovirus proliferation in airway organoids.
RESULTS
HSAEC1-KT, HuLEC-5a and HELF cells cocultured at 10:7:2 self-assembled into airway organoids and maintained long-term proliferation in a RADA16-I hydrogel 3D culture system. The organoids stably expressed the lumen-forming protein KRT8 and the terminal airway markers AQP5 and SPC. Adenoviruses maintained long-term proliferation in this model.
CONCLUSION
An airway-organoid model of adenovirus infection was constructed in vitro from three human lung-derived cell lines on RADA16-I hydrogels. The model has potential as a novel research tool for adenovirus isolation and culture, pathogenesis research, and antiviral drug screening.
Topics: Humans; Peptides; Adenoviridae Infections; Adenoviridae; Organoids; Antiviral Agents; Hydrogels
PubMed: 37727651
DOI: 10.2147/IJN.S413743