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Transplant Infectious Disease : An... Aug 2020Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been...
Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: Multicenter survey of transplant centers in the United States.
BACKGROUND
Adenovirus (AdV) is increasingly recognized as a threat to successful outcomes after allogeneic hematopoietic cell transplantation (allo-HCT). Guidelines have been developed to inform AdV screening and treatment practices, but the extent to which they are followed in clinical practice in the United States is still unknown. The incidence of AdV in the United States is also not well documented. The main objectives of the AdVance US study were thus to characterize current AdV screening and treatment practices in the United States and to estimate the incidence of AdV infection in allo-HCT recipients across multiple pediatric and adult transplant centers.
METHODS
Fifteen pediatric centers and 6 adult centers completed a practice patterns survey, and 15 pediatric centers and four adult centers completed an incidence survey.
RESULTS
The practice patterns survey results confirm that pediatric transplant centers are more likely than adult centers to routinely screen for AdV, and are also more likely to have a preemptive AdV treatment approach compared to adult centers. Perceived risk of AdV infection is a determining factor for whether routine screening and preemptive treatment are implemented. Most pediatric centers screen higher-risk patients for AdV weekly, in blood, and have a preemptive AdV treatment approach. The incidence survey results show that from 2015 to 2017, a total of 1230 patients underwent an allo-HCT at the 15 pediatric transplant centers, and 1815 patients underwent an allo-HCT at the 4 adult transplant centers. The incidences of AdV infection, AdV viremia, and AdV viremia ≥ 1000 copies/mL within 6 months after the first allo-HCT were 23%, 16%, and 9%, respectively, for patients at pediatric centers, and 5%, 3%, and 2%, respectively, for patients at adult centers.
CONCLUSIONS
These findings provide a more recent estimate of the incidence of AdV infection in the United States, as well as a multicenter view of practice patterns around AdV infection screening and intervention criteria, in pediatric and adult allo-HCT recipients.
Topics: Adenoviridae Infections; Adolescent; Adult; Antiviral Agents; Child; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Practice Patterns, Physicians'; Retrospective Studies; Surveys and Questionnaires; Transplant Recipients; Transplantation, Homologous; United States; Viremia
PubMed: 32267590
DOI: 10.1111/tid.13283 -
Journal of Virology Jun 2021Adenoviruses (AdVs) are etiological agents of gastrointestinal, heart, eye, and respiratory tract infections that can be lethal for immunosuppressed people. Many AdVs...
Adenoviruses (AdVs) are etiological agents of gastrointestinal, heart, eye, and respiratory tract infections that can be lethal for immunosuppressed people. Many AdVs use the coxsackievirus and adenovirus receptor (CAR) as a primary receptor. The CAR isoform resulting from alternative splicing that includes the eighth exon, CAR, localizes to the apical surface of polarized epithelial cells and is responsible for the initiation of AdV infection. We have shown that the membrane level of CAR is tightly regulated by two MAGI-1 PDZ domains, PDZ2 and PDZ4, resulting in increased or decreased AdV transduction, respectively. We hypothesized that targeting the interactions between the MAGI-1 PDZ2 domain and CAR would decrease the apical CAR expression level and prevent AdV infection. Decoy peptides that target MAGI-1 PDZ2 were synthesized (TAT-E6 and TAT-NET1). PDZ2 binding peptides decreased CAR expression and reduced AdV transduction. CAR degradation was triggered by the activation of the regulated intramembrane proteolysis (RIP) pathway through a disintegrin and metalloproteinase (ADAM17) and γ-secretase. Further analysis revealed that ADAM17 interacts directly with the MAGI-1 PDZ3 domain, and blocking the PDZ2 domain enhanced the accessibility of ADAM17 to the substrate (CAR). Finally, we validated the efficacy of TAT-PDZ2 peptides in protecting the epithelia from AdV transduction using a novel transgenic animal model. Our data suggest that TAT-PDZ2 binding peptides are novel anti-AdV molecules that act by enhanced RIP of CAR and decreased AdV entry. This strategy has additional translational potential for targeting other viral receptors that have PDZ binding domains, such as the angiotensin-converting enzyme 2 receptor. Adenovirus is a common threat in immunosuppressed populations and military recruits. There are no currently approved treatments/prophylactic agents that protect from most AdV infections. Here, we developed peptide-based small molecules that can suppress AdV infection of polarized epithelia by targeting the AdV receptor, coxsackievirus and adenovirus receptor (CAR). The newly discovered peptides target a specific PDZ domain of the CAR-interacting protein MAGI-1 and decrease AdV transduction in multiple polarized epithelial models. Peptide-induced CAR degradation is triggered by extracellular domain (ECD) shedding through ADAM17 followed by γ-secretase-mediated nuclear translocation of the C-terminal domain. The enhanced shedding of the CAR ECD further protected the epithelium from AdV infection. Taken together, these novel molecules protect the epithelium from AdV infection. This approach may be applicable to the development of novel antiviral molecules against other viruses that use a receptor with a PDZ binding domain.
Topics: 3T3 Cells; ADAM17 Protein; Adaptor Proteins, Signal Transducing; Adenoviridae; Adenoviridae Infections; Amyloid Precursor Protein Secretases; Animals; Cell Adhesion Molecules; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Dogs; Guanylate Kinases; HEK293 Cells; Humans; Madin Darby Canine Kidney Cells; Mice; Protein Domains
PubMed: 33762416
DOI: 10.1128/JVI.00046-21 -
Enfermedades Infecciosas Y... Dec 2023Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7-8% of viral respiratory diseases in children less than 5 years. Differentiation...
INTRODUCTION
Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7-8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem.
MATERIAL AND METHODS
One hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics).
RESULTS
STANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity.
CONCLUSION
STANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.
Topics: Humans; Child; Adenoviridae; Adenoviridae Infections; Respiratory Tract Infections; Polymerase Chain Reaction; Adenoviruses, Human
PubMed: 37076330
DOI: 10.1016/j.eimce.2022.09.015 -
FEBS Letters Jun 2020The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14-kDa polypeptide endowed with important viral regulatory functions. Although... (Review)
Review
The adenovirus (Ad) early region 4 open reading frame 4 (E4orf4) protein is a small 14-kDa polypeptide endowed with important viral regulatory functions. Although deletion of E4orf4 does not have a major effect on Ad replication due to redundancy among many Ad proteins, E4orf4 provides several functions that improve viral replication. E4orf4 contributes to temporal regulation of virus infection by downregulating early viral gene expression and by altering splicing patterns of Ad mRNAs. It also optimizes the cellular environment for Ad replication by activating the mammalian target of rapamycin pathway to increase viral protein production and by impacting the cell cycle. In addition, E4orf4 participates in the inhibition of the host DNA damage response, promoting the ability of Ad to counteract this antiviral defense mechanism. To fulfill these functions, E4orf4 interacts with numerous cellular proteins, including the major E4orf4 partner, protein phosphatase 2A (PP2A). When expressed alone, outside the context of virus infection, E4orf4 induces an evolutionarily conserved, caspase-independent, cancer-selective cell death with many interesting characteristics. This review critically describes E4orf4's contribution to Ad infection and cancer-cell death.
Topics: Adenoviridae Infections; Alternative Splicing; Animals; Cell Cycle; Cell Death; Cytoplasm; DNA Damage; DNA Replication; Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; Neoplasms; Oncolytic Viruses; Viral Proteins
PubMed: 31792953
DOI: 10.1002/1873-3468.13704 -
Journal of Medical Virology Dec 2020Virus associated diarrhea remains one of the leading causes of children morbidity and mortality in Bangladesh. Human bocavirus (HBoV) has been reported as a potential...
Virus associated diarrhea remains one of the leading causes of children morbidity and mortality in Bangladesh. Human bocavirus (HBoV) has been reported as a potential pathogen of children's diarrhea worldwide. However, due to its frequent association with other gastroenteric pathogens, its role as diarrhea causative agent remains to be defined. This study focuses to detect the incidence of HBoV and adenovirus (AdV) and to determine the molecular and epidemiological characteristics of HBoV and AdV. Between January 2015 to January 2019, 290 fecal specimens were collected from diarrheal children in Bangladesh. All fecal specimens were tested for HBoV and AdV by conventional polymerase chain reaction and sequencing methods. HBoV was detected in 7.24% (21 of 290) of the stool samples, as a sole virus in 71.42% (15 of 21) of the positive samples. AdV was detected in 4.82% (14 of 290) of the samples. The most common clinical symptoms of HBoV infected patients were diarrhea (100%) and vomiting (57%). All of the isolates of HBoV were from HBoV1 and AdV were from AdV41, AdV5, AdV7, and AdV8. To the best of our knowledge, this is the first epidemiological and molecular analysis report of HBoV from clinical specimens in Bangladesh. In the future, more studies are needed to clarify the role of HBoV as diarrheal pathogens.
Topics: Humans; Bangladesh; Gastroenteritis; Human bocavirus; Child, Preschool; Male; Female; Infant; Feces; Parvoviridae Infections; Diarrhea; Phylogeny; Adenoviruses, Human; Child; Incidence; Adenovirus Infections, Human; Adenoviridae Infections; Molecular Epidemiology; Polymerase Chain Reaction
PubMed: 32237149
DOI: 10.1002/jmv.25812 -
Viruses Jul 2021Infection has recently started receiving greater attention as an unusual causative/inducing factor of obesity. Indeed, the biological plausibility of infectobesity... (Review)
Review
Infection has recently started receiving greater attention as an unusual causative/inducing factor of obesity. Indeed, the biological plausibility of infectobesity includes direct roles of some viruses to reprogram host metabolism toward a more lipogenic and adipogenic status. Furthermore, the probability that humans may exchange microbiota components (virome/virobiota) points out that the altered response of IFN and other cytokines, which surfaces as a central mechanism for adipogenesis and obesity-associated immune suppression, is due to the fact that gut microbiota uphold intrinsic IFN signaling. Last but not least, the adaptation of both host immune and metabolic system under persistent viral infections play a central role in these phenomena. We hereby discuss the possible link between adenovirus and obesity-related nonalcoholic fatty liver disease (NAFLD). The mechanisms of adenovirus-36 (Ad-36) involvement in hepatic steatosis/NAFLD consist in reducing leptin gene expression and insulin sensitivity, augmenting glucose uptake, activating the lipogenic and pro-inflammatory pathways in adipose tissue, and increasing the level of macrophage chemoattractant protein-1, all of these ultimately leading to chronic inflammation and altered lipid metabolism. Moreover, by reducing leptin expression and secretion Ad-36 may have in turn an obesogenic effect through increased food intake or decreased energy expenditure via altered fat metabolism. Finally, Ad-36 is involved in upregulation of cAMP, phosphatidylinositol 3-kinase, and p38 signaling pathways, downregulation of Wnt10b expression, increased expression of CCAAT/enhancer binding protein-beta, and peroxisome proliferator-activated receptor gamma 2 with consequential lipid accumulation.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Diet, High-Fat; Glucose; Humans; Inflammation; Lipid Metabolism; Lipogenesis; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Signal Transduction
PubMed: 34372491
DOI: 10.3390/v13071285 -
Virology Journal Sep 2022Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and...
Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and conjunctivitis. However, adenovirus infection is rarely associated with central nervous system involvement. Here, we report a fatal viral sepsis and encephalitis in a child caused by a human adenovirus type 7 infection. We detected human adenovirus type 7 in the patient's nasopharyngeal swab, blood, and cerebrospinal fluid. Our findings indicate clinicians should be aware of the possible central nervous system involvement in adenovirus infection.
Topics: Adenoviridae Infections; Adenovirus Infections, Human; Adenoviruses, Human; Child; Encephalitis; Humans; Viremia
PubMed: 36171632
DOI: 10.1186/s12985-022-01886-z -
Viruses Sep 2020Virus-host cell interactions include several skirmishes between the virus and its host, and the DNA damage response (DDR) network is one of their important... (Review)
Review
Virus-host cell interactions include several skirmishes between the virus and its host, and the DNA damage response (DDR) network is one of their important battlegrounds. Although some aspects of the DDR are exploited by adenovirus (Ad) to improve virus replication, especially at the early phase of infection, a large body of evidence demonstrates that Ad devotes many of its proteins, including E1B-55K, E4orf3, E4orf4, E4orf6, and core protein VII, and utilizes varied mechanisms to inhibit the DDR. These findings indicate that the DDR would strongly restrict Ad replication if allowed to function efficiently. Various Ad serotypes inactivate DNA damage sensors, including the Mre11-Rad50-Nbs1 (MRN) complex, DNA-dependent protein kinase (DNA-PK), and Poly (ADP-ribose) polymerase 1 (PARP-1). As a result, these viruses inhibit signaling via DDR transducers, such as the ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) kinases, to downstream effectors. The different Ad serotypes utilize both shared and distinct mechanisms to inhibit various branches of the DDR. The aim of this review is to understand the interactions between Ad proteins and the DDR and to appreciate how these interactions contribute to viral replication.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Ataxia Telangiectasia Mutated Proteins; DNA Damage; Humans; Signal Transduction; Virus Replication
PubMed: 32906746
DOI: 10.3390/v12090996 -
Veterinary Research Apr 2021Infectious bursal disease virus (IBDV) and fowl adenovirus serotype 4 (FAdV-4) cause infectious bursal disease (IBD) and hydropericardium-hepatitis syndrome,...
Infectious bursal disease virus (IBDV) and fowl adenovirus serotype 4 (FAdV-4) cause infectious bursal disease (IBD) and hydropericardium-hepatitis syndrome, respectively. Recently, studies have reported co-infections of poultry with IBDV and FAdV-4, which is an important problem in the poultry industry. Here, the variant IBDV strain ZD-2018-1 and FAdV-4 isolate HB1501 were used to assess the pathogenicity of co-infection in 1-day-old specific pathogen-free (SPF) chickens. Compared with chickens infected with only FAdV-4, those coinfected with IBDV and FAdV-4 showed enhanced clinical symptoms, higher mortality, more severe tissue lesions, and higher biochemical index levels. Furthermore, the expression of interleukin (IL)-6, IL-1β, and interferon-γ mRNAs in the IBDV-FAdV-4 coinfected chickens was delayed, and the antibody response levels were significantly lower in those birds compared with the FAdV-4-infected chickens. These results indicate that co-infection with variant IBDV ZD-2018-1 and FAdV-4 HB1501 could significantly promote the pathogenicity of FAdV-4 and reduce the immune response in chickens. This study provides the foundation for further investigation of the interaction mechanism in IBDV and FAdV-4 co-infection.
Topics: Adenoviridae Infections; Animals; Aviadenovirus; Birnaviridae Infections; Chickens; Coinfection; Immunity, Innate; Infectious bursal disease virus; Poultry Diseases; Specific Pathogen-Free Organisms
PubMed: 33926543
DOI: 10.1186/s13567-021-00932-y -
Influenza and Other Respiratory Viruses Jan 2021HAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life-threatening respiratory disease can occur. Pneumonia is one of the...
BACKGROUND
HAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life-threatening respiratory disease can occur. Pneumonia is one of the more serious types of HAdV-induced respiratory disease in children. In this study, we determined the prevalence and genotype of HAdVs among children hospitalized with pneumonia in Guangzhou, China.
METHODS
Nasopharyngeal swabs (NPSs) were collected from children hospitalized with pneumonia in Guangzhou, China, from January 2013 to June 2019. HAdVs were detected by real-time polymerase chain reaction assay, and hexon, fiber, and penton gene were amplified and used for phylogenetic analysis. Epidemiological data were analyzed using SPSS16.0 software.
RESULTS AND CONCLUSIONS
A total of 1778 children hospitalized with pneumonia were enrolled. The overall HAdV detection rate was 3.26%. And the yearly detection rate varied from around 2.5% in 2013-2017 to around 6% in 2018-2019. Children >5 years had the highest HAdV infection rate. 92.86% of HAdV sequences obtained in this study were belonged to species B, and no recombination was observed. HAdV-B7 and HAdV-B3 were the common types detected in the study period, with the predominant HAdV genotype shifted from HAdV-B3 in 2015-2016 to HAdV-B7 in 2017-2018. The discrepancies in HAdV detection rates in different study period and changes of HAdV predominant types over time highlighted the importance of continued surveillance.
Topics: Adenoviridae Infections; Adenovirus Infections, Human; Adenoviruses, Human; Child; China; Genotype; Humans; Phylogeny; Pneumonia; Respiratory Tract Infections; Sequence Analysis, DNA
PubMed: 32761743
DOI: 10.1111/irv.12782