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MMWR. Morbidity and Mortality Weekly... May 2022During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon...
During October-November 2021, clinicians at a children's hospital in Alabama identified five pediatric patients with severe hepatitis and adenovirus viremia upon admission. In November 2021, hospital clinicians, the Alabama Department of Public Health, the Jefferson County Department of Health, and CDC began an investigation. This activity was reviewed by CDC and conducted consistent with applicable federal law and CDC policy.
Topics: Acute Disease; Adenoviridae Infections; Alabama; Child; Hepatitis; Humans; Public Health
PubMed: 35511732
DOI: 10.15585/mmwr.mm7118e1 -
Poultry Science Nov 2020Outbreaks of inclusion body hepatitis (IBH) and adenoviral gizzard erosion have been anecdotally reported in Greece since approximately 2011. However, a relevant...
Outbreaks of inclusion body hepatitis (IBH) and adenoviral gizzard erosion have been anecdotally reported in Greece since approximately 2011. However, a relevant increase in clinical outbreaks compatible with IBH has been described since 2014. Unfortunately, with limited exceptions, only serological assays were performed, and involved strains were not properly characterized. In the present study, 35 outbreaks were investigated in the period between July 2017 and February 2018 in Greece. In addition to clinical and histopathological diagnosis, fowl adenovirus (FAdV) presence was investigated by PCR and sequencing. Thirty-four out of 35 samples tested FAdV positive. Twenty-nine (85.29%) and 5 (14.71%) strains were classified as FAdV-E and FAdV-D, respectively. Fowl adenovirus-E strains were genetically homogeneous and formed an independent cluster of Greek-only sequences, including the sole previously available sequence, suggesting the prolonged circulation of this species in Greece. On the contrary, FAdV-D strains were more heterogeneous and closely related to strains sampled in other European countries, testifying the occurrence of multiple introduction events. The evaluation of phylogenetic relationships, geographic clustering, age of infection, and origin of the broiler breeder flocks suggests that both vertical and horizontal transmission are important in FAdV epidemiology in Greece and highlights the limited efficacy of currently implemented control measures. Of note, a significantly higher mortality was observed in precociously infected flocks, likely because of the higher susceptibility of younger animals. This evidence stresses the need of preventing vertical and/or early infection to limit the economic impact of adenovirus-induced diseases.
Topics: Adenoviridae Infections; Animals; Aviadenovirus; Chickens; Europe; Greece; Molecular Epidemiology; Phylogeny; Poultry Diseases
PubMed: 33142516
DOI: 10.1016/j.psj.2020.07.019 -
Acta Paediatrica (Oslo, Norway : 1992) Mar 2022Adenovirus infections are exceedingly common in childhood. However, little is known of the clinical characteristics of children admitted with severe infection to the...
AIM
Adenovirus infections are exceedingly common in childhood. However, little is known of the clinical characteristics of children admitted with severe infection to the paediatric intensive care unit (PICU).
METHODS
Clinical data on children hospitalised with adenovirus infection between January 2005 and March 2020 were collected. We compared data between children hospitalised in the PICU and those who were not in a 1:2 ratio.
RESULTS
During the study period, 69 children with adenovirus infection were admitted to the PICU, representing 5% of all hospitalised children with adenovirus. Thirty-four (49%) were previously healthy children. Mortality occurred in 5 patients, and all had an underlying illness. Cidofovir was used in 21 children, including 11 who were previously healthy. No side effects were attributed to the treatment. During 2005-2014, viral co-infection rates were 42% in the PICU group and 11% in the control group (p = 0.002). However, during 2015-2020, when the viral panel became widespread in our institution, the rates of co-infection were similar in the two groups (32% and 34%, p = 1.0).
CONCLUSION
Our findings suggest that adenovirus may present as a serious, life-threatening disease even in previously healthy children.
Topics: Adenoviridae; Adenoviridae Infections; Child; Hospitalization; Humans; Infant; Intensive Care Units, Pediatric; Retrospective Studies
PubMed: 34862832
DOI: 10.1111/apa.16207 -
PloS One 2018Viral infections cause large problems in the world and deeper understanding of the disease mechanisms is needed. Here we present an analytical strategy to investigate...
Viral infections cause large problems in the world and deeper understanding of the disease mechanisms is needed. Here we present an analytical strategy to investigate the host cell protein changes during human adenovirus type 2 (HAdV-C2 or Ad2) infection of lung fibroblasts by stable isotope labelling of amino acids in cell culture (SILAC) and nanoLC-MS/MS. This work focuses on early phase of infection (6 and 12 h post-infection (hpi)) but the data is combined with previously published late phase (24 and 36 hpi) proteomics data to produce a time series covering the complete infection. As many as 2169 proteins were quantitatively monitored from 6 to 36 hpi, while some proteins were time-specific. After applying different filter criteria, 2027 and 2150 proteins were quantified at 6 and 12 hpi and among them, 431 and 544 were significantly altered at the two time points. Pathway analysis showed that the De novo purine and pyrimidine biosynthesis, Glycolysis and Cytoskeletal regulation by Rho GTPase pathways were activated early during infection while inactivation of the Integrin signalling pathway started between 6 and 12 hpi. Moreover, upstream regulator analysis predicted MYC to be activated with time of infection and protein and RNA data for genes controlled by this transcription factor showed good correlation, which validated the use of protein data for this prediction. Among the identified phosphorylation sites, a group related to glycolysis and cytoskeletal reorganization were up-regulated during infection. The results show specific aspects on how the host cell proteins, the final products in the genetic information flow, are influenced by Ad2 infection, which would be overlooked if only knowledge derived from mRNA data is considered.
Topics: Adenoviridae Infections; Adenoviruses, Human; Amino Acids; Cell Line; Host Microbial Interactions; Humans; Kinetics; Metabolic Networks and Pathways; Phosphopeptides; Proteome; Proteomics; RNA, Messenger; Tandem Mass Spectrometry; Transcription Factors
PubMed: 30252905
DOI: 10.1371/journal.pone.0204522 -
Ophthalmology Sep 2018To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To determine host and pathogen factors predictive of outcomes in a large clinical cohort with keratoconjunctivitis.
DESIGN
Retrospective analyses of the clinical and molecular data from a randomized, controlled, masked trial for auricloscene for keratoconjunctivitis (NVC-422 phase IIB, NovaBay; clinicaltrials.gov identifier, NCT01877694).
PARTICIPANTS
Five hundred participants from United States, India, Brazil, and Sri Lanka with clinical diagnosis of keratoconjunctivitis and positive rapid test results for adenovirus.
METHODS
Clinical signs and symptoms and bilateral conjunctival swabs were obtained on days 1, 3, 6, 11, and 18. Polymerase chain reaction (PCR) analysis was performed to detect and quantify adenovirus in all samples. Regression models were used to evaluate the association of various variables with keratoconjunctivitis outcomes. Time to resolution of each symptom or sign was assessed by adenoviral species with Cox regression.
MAIN OUTCOME MEASURES
The difference in composite scores of clinical signs between days 1 and 18, mean visual acuity change between days 1 and 18, and time to resolution of each symptom or sign.
RESULTS
Of 500 participants, 390 (78%) showed evidence of adenovirus by PCR. Among adenovirus-positive participants, adenovirus D species was most common (63% of total cases), but a total of 4 species and 21 different types of adenovirus were detected. Adenovirus D was associated with more severe signs and symptoms, a higher rate of subepithelial infiltrate development, and a slower decline in viral load compared with all other adenovirus species. The clinical courses of all patients with non-adenovirus D species infection and adenovirus-negative keratoconjunctivitis were similar. Mean change in visual acuity between days 1 and 18 was a gain of 1.9 letters; worse visual outcome was associated with older age.
CONCLUSIONS
A substantial proportion of keratoconjunctivitis is not associated with a detectable adenovirus. The clinical course of those with adenovirus D keratoconjunctivitis is significantly more severe than those with non-adenovirus D species infections or adenovirus-negative keratoconjunctivitis; high viral load at presentation and non-United States origin of participants is associated with poorer clinical outcome.
Topics: Adenoviridae; Adenoviridae Infections; Adolescent; Adult; Aged; Aged, 80 and over; Brazil; Child; Child, Preschool; DNA, Viral; Eye Infections, Viral; Female; Follow-Up Studies; Humans; Incidence; India; Infant; Keratoconjunctivitis; Male; Middle Aged; Polymerase Chain Reaction; Retrospective Studies; Sri Lanka; United States; Young Adult
PubMed: 29602567
DOI: 10.1016/j.ophtha.2018.02.016 -
The Journal of Pediatrics Aug 2023To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was...
OBJECTIVE
To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years.
STUDY DESIGN
We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021.
RESULTS
Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively.
CONCLUSIONS
The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.
Topics: Humans; Child; Adenoviridae; Retrospective Studies; Incidence; COVID-19; Hepatitis; Adenoviridae Infections
PubMed: 37088181
DOI: 10.1016/j.jpeds.2023.113439 -
The Israel Medical Association Journal... Aug 2016
Topics: Adenoviridae; Adenoviridae Infections; Antiviral Agents; Child; Child, Preschool; Humans; Male; Meningoencephalitis
PubMed: 28471592
DOI: No ID Found -
Virology Feb 2017The abundance and accessibility of a primary virus receptor are critical factors that impact the susceptibility of a host cell to virus infection. The Coxsackievirus and...
The abundance and accessibility of a primary virus receptor are critical factors that impact the susceptibility of a host cell to virus infection. The Coxsackievirus and adenovirus receptor (CAR) has two transmembrane isoforms that occur due to alternative splicing and differ in localization and function in polarized epithelia. To determine the relevance of isoform-specific expression across cell types, the abundance and localization of both isoforms were determined in ten common cell lines, and correlated with susceptibility to adenovirus transduction relative to polarized primary human airway epithelia. Data show that the gene and protein expression for each isoform of CAR varies significantly between cell lines and polarization, as indicated by high transepithelial resistance, is inversely related to adenovirus transduction. In summary, the variability of polarity and isoform-specific expression among model cells are critical parameters that must be considered when evaluating the clinical relevance of potential adenovirus-mediated gene therapy and anti-adenovirus strategies.
Topics: Adenoviridae; Adenoviridae Infections; Cell Line; Cell Polarity; Cells, Cultured; Epithelial Cells; Humans; Protein Isoforms; Receptors, Virus; Respiratory System; Transduction, Genetic
PubMed: 28049062
DOI: 10.1016/j.virol.2016.12.020 -
Virology Aug 2022In the adenovirus-infected cells, virus mRNAs are selectively exported to the cytoplasm by virus early gene products to facilitate virus replication. We previously...
In the adenovirus-infected cells, virus mRNAs are selectively exported to the cytoplasm by virus early gene products to facilitate virus replication. We previously showed AU-rich elements (AREs) containing mRNAs are exported to the cytoplasm and stabilized in infected cells. Here, we analyzed ribonucleoprotein (RNP) granules in the cytoplasm that are involved in mRNA degradation to elucidate the mechanism of ARE-mRNA stabilization in adenovirus infected cells. Our findings showed that processing bodies (PBs) aggregate, then almost all PBs are translocated to aggresomes formed by adenoviral gene products during the late phase of infection. Furthermore, E4orf3 was required for the PBs translocation, and the same domains of E4orf3-mutants required to change the form of promyelocytic leukemia bodies were also needed for PBs translocation. Luciferase activity showed that these domains were critical for miRNA- and ARE-mediated mRNA decay. These findings suggest that adenovirus changes the behavior of PBs to prevent ARE-mRNA downregulation.
Topics: Adenoviridae; Adenoviridae Infections; Cytoplasm; Humans; Processing Bodies; RNA, Messenger; Viral Proteins; Virus Replication
PubMed: 35779334
DOI: 10.1016/j.virol.2022.06.009 -
Immunology and Cell Biology Jan 2017Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and...
Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88 mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45 cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection.
Topics: A549 Cells; Adenoviridae; Adenoviridae Infections; Animals; Cornea; Female; Humans; Keratitis; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; Receptors, Interleukin-1; Toll-Like Receptor 2; Toll-Like Receptor 9; Virus Internalization; src-Family Kinases
PubMed: 27528076
DOI: 10.1038/icb.2016.73