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Frontiers in Immunology 2023Human adenovirus (HAdV) is a common respiratory virus, which can lead to severe pneumonia in children and immunocompromised persons, and canonical inflammasomes are...
INTRODUCTION
Human adenovirus (HAdV) is a common respiratory virus, which can lead to severe pneumonia in children and immunocompromised persons, and canonical inflammasomes are reported to be involved in anti-HAdV defense. However, whether HAdV induced noncanonical inflammasome activation has not been explored. This study aims to explore the broad roles of noncanonical inflammasomes during HAdV infection to investigate the regulatory mechanism of HAdV-induced pulmonary inflammatory damage.
METHODS
We mined available data on GEO database and collected clinical samples from adenovirus pneumonia pediatric patients to investigate the expression of noncanonical inflammasome and its clinical relevance. An cell model was employed to investigate the roles of noncanonical inflammasomes in macrophages in response to HAdV infection.
RESULTS
Bioinformatics analysis showed that inflammasome-related genes, including caspase-4 and caspase-5, were enriched in adenovirus pneumonia. Moreover, caspase-4 and caspase-5 expression levels were significantly increased in the cells isolated from peripheral blood and broncho-alveolar lavage fluid (BALF) of pediatric patients with adenovirus pneumonia, and positively correlated with clinical parameters of inflammatory damage. experiments revealed that HAdV infection promoted caspase-4/5 expression, activation and pyroptosis in differentiated THP-1 (dTHP-1) human macrophages via NF-κB, rather than STING signaling pathway. Interestingly, silencing of caspase-4 and caspase-5 in dTHP-1 cells suppressed HAdV-induced noncanonical inflammasome activation and macrophage pyroptosis, and dramatically decreased the HAdV titer in cell supernatants, by influencing virus release rather than other stages of virus life cycle.
DISCUSSION
In conclusion, our study demonstrated that HAdV infection induced macrophage pyroptosis by triggering noncanonical inflammasome activation via a NF-kB-dependent manner, which may explore new perspectives on the pathogenesis of HAdV-induced inflammatory damage. And high expression levels of caspase-4 and caspase-5 may be a biomarker for predicting the severity of adenovirus pneumonia.
Topics: Humans; Child; Inflammasomes; Pyroptosis; Adenovirus Infections, Human; Macrophages; NF-kappa B; Caspases; Pneumonia, Viral; Adenoviridae Infections
PubMed: 37180156
DOI: 10.3389/fimmu.2023.1169968 -
Trends in Molecular Medicine Jan 2023The consequences of human adenovirus (HAdV) infections are generally mild. However, despite the perception that HAdVs are harmless, infections can cause severe disease... (Review)
Review
The consequences of human adenovirus (HAdV) infections are generally mild. However, despite the perception that HAdVs are harmless, infections can cause severe disease in certain individuals, including newborns, the immunocompromised, and those with pre-existing conditions, including respiratory or cardiac disease. In addition, HAdV outbreaks remain relatively common events and the recent emergence of more pathogenic genomic variants of various genotypes has been well documented. Coupled with evidence of zoonotic transmission, interspecies recombination, and the lack of approved AdV antivirals or widely available vaccines, HAdVs remain a threat to public health. At the same time, the detailed understanding of AdV biology garnered over nearly 7 decades of study has made this group of viruses a molecular workhorse for vaccine and gene therapy applications.
Topics: Infant, Newborn; Humans; Adenoviridae; Adenovirus Infections, Human; Adenoviruses, Human; Genomics; Genotype; Phylogeny; Respiratory Tract Infections
PubMed: 36336610
DOI: 10.1016/j.molmed.2022.10.001 -
FEBS Letters Jun 2020The coxsackievirus and adenovirus receptor (CAR) is an essential multifunctional cellular protein that is only beginning to be understood. CAR serves as a receptor for... (Review)
Review
The coxsackievirus and adenovirus receptor (CAR) is an essential multifunctional cellular protein that is only beginning to be understood. CAR serves as a receptor for many adenoviruses, human group B coxsackieviruses, swine vesicular disease virus, and possibly other viruses. While named for its function as a viral receptor, CAR is also involved in cell adhesion, immune cell activation, synaptic transmission, and signaling. Knockout mouse models were first to identify some of these biological functions; however, tissue-specific model systems have shed light on the complexity of different CAR isoforms and their specific activities. Many of these functions are mediated by the large number of interacting proteins described so far, and several new putative interactions have recently been discovered. As antiviral and gene therapy strategies that target CAR continue to emerge, future work poised to understand the biological implications of manipulating CAR in vivo is critical.
Topics: Adenoviridae Infections; Alternative Splicing; Animals; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Gene Expression Regulation, Developmental; Humans; Mice; Protein Isoforms
PubMed: 32298477
DOI: 10.1002/1873-3468.13794 -
PLoS Neglected Tropical Diseases Feb 2023Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human adenovirus (HAdV) is a major pathogen that causes acute respiratory tract infections (ARTI) and is frequently associated with outbreaks. The HAdV prevalence and the predominant types responsible for ARTI outbreaks remains obscure in China.
METHODS
A systematic review was performed to retrieve literature that reported outbreaks or etiological surveillance of HAdV among ARTI patients in China from 2009 to 2020. Patient information was extracted from the literature to explore the epidemiological characteristics and clinical manifestations of the infection of various HAdV types. The study is registered with PROSPERO, CRD42022303015.
RESULTS
A total of 950 articles (91 about outbreaks and 859 about etiological surveillance) meeting the selection criteria were included. Predominant HAdV types from etiological surveillance studies differed from those in outbreak events. Among 859 hospital-based etiological surveillance studies, positive detection rates of HAdV-3 (32.73%) and HAdV-7 (27.48%) were significantly higher than other virus types. While nearly half (45.71%) of outbreaks were caused by HAdV-7 with an overall attack rate of 22.32% among the 70 outbreaks for which the HAdVs were typed by the meta-analysis. Military camp and school were main outbreak settings with significantly different seasonal pattern and attack rate, where HAdV-55 and HAdV-7 were identified as the leading type, respectively. Clinical manifestations mainly depended on the HAdV types and patient's age. HAdV-55 infection tends to develop into pneumonia with poorer prognosis, especially in children <5 years old.
CONCLUSIONS
This study improves the understanding of epidemiological and clinical features of HAdV infections and outbreaks with different virus types, and helps to inform future surveillance and control efforts in different settings.
Topics: Child; Humans; Child, Preschool; Prevalence; Phylogeny; Adenoviridae Infections; China; Respiratory Tract Infections; Adenovirus Infections, Human; Adenoviruses, Human
PubMed: 36812245
DOI: 10.1371/journal.pntd.0011151 -
The Israel Medical Association Journal... Jul 2021Adenovirus infections are prevalent in children. They usually cause a mild self-limited disease. However, this infection can be associated with considerable morbidity...
BACKGROUND
Adenovirus infections are prevalent in children. They usually cause a mild self-limited disease. However, this infection can be associated with considerable morbidity and mortality in specific populations, especially among immunocompromised children. Children with Down syndrome are susceptible to a higher frequency and increased severity of viral infections. Little is known about the severity and clinical course of adenovirus infections in children with Down syndrome.
OBJECTIVES
To characterize hospitalized children diagnosed with Down syndrome and presenting with adenovirus infection.
METHODS
We performed a retrospective review of children admitted with adenovirus from January 2005 to August 2014 from a single tertiary pediatric medical center in Israel. Data were compared between patients with and without Down syndrome.
RESULTS
Among the 486 hospitalized children with adenoviral infection, 11 (2.28%) were diagnosed with Down syndrome. We found that children with Down syndrome were more likely to experience a higher incidence of complications (18.2% vs. 2.4%, P = 0.008), a higher rate of admissions to the intensive care unit (36.4% vs. 2.4%, P < 0.001), and more prolonged hospitalizations (17 ± 15.9 days compared to 4.46 ± 3.16, P = 0.025).
CONCLUSIONS
Children with Down syndrome who were hospitalized with adenovirus infection represent a high-risk group and warrant close monitoring. If a vaccine for adenovirus becomes available, children with Down syndrome should be considered as candidates.
Topics: Adenoviridae; Adenovirus Infections, Human; Child, Preschool; Critical Care; Down Syndrome; Female; Hospitalization; Hospitals, Pediatric; Humans; Incidence; Israel; Length of Stay; Male; Risk Assessment; Severity of Illness Index; Tertiary Care Centers
PubMed: 34251123
DOI: No ID Found -
Viruses Jul 2020Many 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... (Review)
Review
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.
Topics: Adenoviridae; Adenoviridae Infections; Animals; Capsid; Capsid Proteins; Cryoelectron Microscopy; Humans; Virus Replication
PubMed: 32630840
DOI: 10.3390/v12070718 -
FEBS Letters Dec 2019The DNA genome of eukaryotic cells is compacted by histone proteins within the nucleus to form chromatin. Nuclear-replicating viruses such as adenovirus have evolved... (Review)
Review
The DNA genome of eukaryotic cells is compacted by histone proteins within the nucleus to form chromatin. Nuclear-replicating viruses such as adenovirus have evolved mechanisms of chromatin manipulation to promote infection and subvert host defenses. Epigenetic factors may also regulate persistent adenovirus infection and reactivation in lymphoid tissues. In this review, we discuss the viral proteins E1A and protein VII that interact with and alter host chromatin, as well as E4orf3, which separates host chromatin from sites of viral replication. We also highlight recent advances in chromatin technologies that offer new insights into virus-directed chromatin manipulation. Beyond the role of chromatin in the viral replication cycle, we discuss the nature of persistent viral genomes in lymphoid tissue and cell lines, and the potential contribution of epigenetic signals in maintaining adenovirus in a quiescent state. By understanding the mechanisms through which adenovirus manipulates host chromatin, we will understand new aspects of this ubiquitous virus and shed light on previously unknown aspects of chromatin biology.
Topics: Adenovirus E1A Proteins; Adenovirus E4 Proteins; Adenovirus Infections, Human; Adenoviruses, Human; Capsid Proteins; Cell Nucleus; Chromatin; Epigenesis, Genetic; Host-Pathogen Interactions; Humans; Virus Replication
PubMed: 31769503
DOI: 10.1002/1873-3468.13697 -
Viruses Aug 2023Astroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals...
Astroviruses (AstV) and adenoviruses (AdV) are associated with diarrhoea in young animals. However, the epidemiology and genetic diversity of AstVs and AdVs in animals is not well studied. Hence, the present study was conducted to detect and characterize AstVs and AdVs in calves, piglets and puppies from Western Maharashtra, India. Out of the processed porcine (48), canine (80), and bovine (65) faecal samples, the porcine AstV (PAstV), bovine AstV (BAstV), canine AstV (CAstV), and porcine AdV (PAdV) were detected in 12.5%, 7.69%, 3.75% and 4.1% of samples, respectively. In the RNA-dependent RNA polymerase region-based phylogenetic analysis, the detected BAstV strains grouped with MAstV-28, MAstV-33, and MAstV-35, CAstV strains belonged to MAstV-5; PAstV strains belonged to MAstV-24, MAstV-26, and MAstV-31. However, in hexon gene-based phylogeny, both the detected PAdV were of genotype 3, exhibiting 91.9-92.5% nucleotide identity with Ivoirian and Chinese strains. The study reports first-time BAstVs from calves and PAdV-3 from piglets in India. The study revealed diversity in the circulation of AstVs in tested animals and AdVs in pigs, and suggested that they alone might be associated with other diarrhoea or in combination with other enteric pathogens, thus highlighting the necessity of extensive epidemiological investigations to develop diagnostic tools and control measures.
Topics: Animals; Cattle; Dogs; Swine; Adenoviridae; Phylogeny; India; Adenoviridae Infections; Astroviridae; Canidae; Diarrhea
PubMed: 37632021
DOI: 10.3390/v15081679 -
Pediatrics and Neonatology Jul 2023Human adenoviruses are the most common pathogens to be isolated from cases of pediatric intussusception. However, the specific clinical characteristics of pediatric... (Review)
Review
BACKGROUND
Human adenoviruses are the most common pathogens to be isolated from cases of pediatric intussusception. However, the specific clinical characteristics of pediatric intussusception associated with adenovirus infection are poorly known.
METHODS
We reviewed the medical records of pediatric patients (≤18 years of age) with intussusception treated between January 2014 and December 2020. We enrolled patients with febrile episodes, 27 with and 29 without adenovirus infections (the latter serving as control group). The demographic data, clinical characteristics, and the diagnoses and management strategies were evaluated.
RESULTS
The adenovirus group exhibited a significantly longer febrile duration (4.3 ± 1.9 vs. 3.3 ± 1.1 days, p = 0.020) than the control group, with an odds ratio (OR) of 5.098 (95% confidence interval [CI] 1.223-21.254, p = 0.025). The recurrence rates were 48.1% and 13.8% in the two groups (OR 5.804; 95% CI: 1.585-21.245, p = 0.008). Most adenoviruses were non-enteric (85.2%).
CONCLUSION
Adenovirus-related intussusception is associated with a longer febrile period and a higher rate of intussusception recurrence. It is recommended that patients suspected of adenovirus-related intussusception should be observed for longer than others prior to discharge.
Topics: Humans; Child; Infant; Intussusception; Adenoviridae Infections; Adenoviruses, Human; Risk Factors; Odds Ratio; Retrospective Studies
PubMed: 36641360
DOI: 10.1016/j.pedneo.2022.03.024 -
The Pediatric Infectious Disease Journal Dec 2020Intussusception is the leading cause of acute intestinal obstruction in infants. Intussusception is mostly idiopathic, but infectious pathogens are sometimes implicated.... (Review)
Review
BACKGROUND
Intussusception is the leading cause of acute intestinal obstruction in infants. Intussusception is mostly idiopathic, but infectious pathogens are sometimes implicated. In addition, live oral rotavirus vaccines have been associated with intussusception.
METHODS
We searched the literature published between January 1, 1990, and March 16, 2020, to describe the association between intussusception among infants and young children and various pathogens, particularly adenovirus and wild rotavirus. We tallied the number of evaluations reporting a statistically significant positive association, no association and a protective association by pathogen, using any statistical method. We also calculated the median reported odds ratios (OR) of intussusception with adenovirus and rotavirus.
RESULTS
We identified 3793 records on intussusception from the literature; 17 evaluations from 15 countries that evaluated 52 pathogens were included in the analysis. All 14 evaluations of adenovirus reported a statistically significant positive association with intussusception; the median OR from 9 evaluations was 3.7 (interquartile range, 3.3, 8.2). Nine of 12 evaluations assessing rotavirus found no statistically significant association, 1 found a positive association and 2 reported a protective effect; the median OR from 12 evaluations was 0.9 (interquartile range, 0.2, 1.8). No consistent relationship was observed between any other pathogens and intussusception.
CONCLUSIONS
We documented a consistent association of intussusception with adenovirus, but no relationship between wild-type rotavirus and intussusception. Future research should focus on better understanding the mechanisms of intussusception with infectious pathogens, including following a rotavirus vaccination.
Topics: Adenoviridae; Adenoviridae Infections; Child, Preschool; Humans; Infant; Intussusception; Rotavirus; Rotavirus Infections
PubMed: 33060518
DOI: 10.1097/INF.0000000000002860