Search Results (161)

Extracellular vesicles (EVs) are rapidly gaining recognition as critical mediators of inter-cellular communication during viral infections. To contribute to fill the gap in knowledge regarding the role of EVs in adenovirus infection, we used human adenovirus type 4 of species Mastadenovirus exoticum (HAdV-E4), a prevalent respiratory and ocular pathogen, and characterized the cargo and biological properties of EVs released by HAdV-E4-infected A549 lung epithelial cells at a pre-lytic stage of infection. Using immunocapture-based isolation and multi-omics approaches, we found that infection profoundly alters the EV uploaded proteome and small non-coding RNA repertoire. Mass spectrometry identified 268 proteins unique to EVs purified from infected cells (AdV-EVs), with enrichment in pathways supporting vesicle trafficking and viral protein translation, and importantly also a few virus-encoded proteins. A small RNA transcriptome analysis showed differential uploading in AdV-EVs of various small non-coding RNAs, including snoRNAs, as well as the presence of virus associated RNAs I and II. Notably, AdV-EVs contained viral genomic DNA and could initiate productive infection upon delivery to naïve cells in the absence of detectable viral particles. Our data suggest that EVs released during the HAdV-E4 infection may serve as vehicles for non-lytic viral dissemination and highlight their possible role in intra-host dissemination Full article

The combination of rGO-FETs (reduced Graphene Oxide Field-Effect Transistors) and DNA-oligonucleotide aptamers to sense analytes has been shown to be a promising technological approach, achieving high sensitivity and selectivity. With human adenovirus type 5 (HAdV-5) particles as the target, we here demonstrate the application of the aptamer/FET combination for detection of this medically and biotechnologically relevant viral vector. A focused anti-HAdV-5 aptamer library was evolved in a nine-round SELEX process, allowing for the specific fluorescent labeling of HAdV-5 and related subtypes. Moreover, this library was already sufficient to serve as the binding entity on a gFET sensor for sensitive quantification of the virus particles. Adenoviruses have been widely used as gene delivery vectors for gene therapy and genetic vaccination. The use of adenoviral vectors within the vaccination campaign against COVID-19 emphasized the need for robust biotechnological production processes, which additionally require sensitive product formation monitoring. We believe that these type of gFET-based aptasensors can serve as the technological monitoring basis in virus production processes in the near future. Full article

Replication-defective adenoviruses are widely used as vectors for vaccines, but their efficacy may be compromised by the prevalence of pre-existing neutralizing antibodies from natural infections or prior vaccination with adenovirus-based vaccines. To overcome these limitations, less common human adenovirus (HAdV) types and simian adenoviruses (SAdV) have been explored as alternative vectors to the widely prevalent HAdV-C5. Despite their importance, there is limited information on the epidemiology of adenovirus immunity in many countries and geographical regions, including Mexico. In this study, we analyzed 2488 serum samples from healthy adults across all 32 states of Mexico to assess the prevalence of both total and neutralizing antibodies against various HAdV types from species A-F, and three related SAdVs. Our findings indicate a high prevalence of neutralizing antibodies against HAdV-C5 and HAdV-C6, with significant cross-reactivity observed among related adenoviruses. Notably, HAdV-D26 exhibited a lower prevalence of neutralizing antibodies, suggesting its potential suitability as a vector for vaccine development in populations with high pre-existing immunity to more common HAdV types. These results provide critical insights for optimizing adenovirus-based vaccine strategies in Mexico. Full article

Since December 2019, the COVID-19 pandemic caused by SARS-CoV-2 has reached approximately 769 million people, leading to more than 7 million deaths worldwide. Faced with the possibility of other respiratory pathogens co-infecting patients and modifying their clinical response to SARS-CoV-2, some researchers have explored this line of investigation. The relationship between these co-infections remains unclear, underscoring the need to deepen our understanding of interactions among pathogens and between pathogens and the host. Thus, the present study employed RT-qPCR to assess the presence of Human Adenovirus (HAdV), Influenza A (Flu A), Influenza B (Flu B), Human Metapneumovirus (HMPV), Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV), and Parainfluenza Virus (PIV). Nasopharyngeal samples (187) from adult patients exhibiting respiratory symptoms were collected between February 2021 and November 2022 at the University Hospital Polydoro Ernani de São Thiago in Florianópolis, SC, Brazil. The present findings revealed that 25.16% of samples tested positive for non-SARS-CoV-2 respiratory viruses (29.8%—HRV; 5.3%—PIV; 4.3%—RSV; and 1.1%—HMPV). In the 74.84% of SARS-CoV-2-positive patients, co-infection was observed in 9.7% of patients, with 7.5% being HRV, 1.1% HAdV, and 1.1% Influenza A. Since co-infections can potentially alter patient prognoses and impact local epidemiological dynamics, this study highlights the significance of ongoing monitoring and epidemiological assessment through genomic surveillance of other clinically relevant respiratory pathogens. Full article

CrAssphage, a bacteriophage that infects human gut-associated Bacteroides spp., has emerged as a potential anthropogenic fecal pollution indicator in environmental matrices. This study investigated the presence and concentration of crAssphages in bivalve mollusks (oysters and mussels) marketed in three cities in the state of Rio de Janeiro, Brazil, sampled from January to December 2022. CrAssphages were detected during the study period in 66.7% (48/72) of sampled oysters and 54.8% (34/62) of sampled mussels, at median concentrations of 1.9 × 10⁴ and 4.2 × 10⁴ genome copies (GC)/g, respectively. These levels were 1–2 log₁₀ higher than those observed for major human enteric viruses, including norovirus genogroups GI and GII, sapovirus, human mastadenovirus (HAdV), rotavirus A, human astrovirus (HAstV), and hepatitis A virus. CrAssphage specificity and sensitivity were calculated for all viruses. Moderate correlations between crAssphage (log₁₀ GC/g) and norovirus GI and GII, HAdV, SaV, and HAstV (Spearman’s rho = 0.581–0.464, p < 0.001) were observed in mussels. Altogether, the data support the use of crAssphage as a molecular indicator of human viral contamination in shellfish, with potential application in routine environmental and food safety monitoring in production areas. Full article

Human adenoviruses (HAdVs) are pathogens causing different illnesses, particularly in pediatric and immunocompromised patients in developed countries. The clinical spectrum of HAdV-infections ranges from mild to severe, and the clinical presentation varies widely. Certain HAdVs types, including types B3, E4, B7, B14, B21, G55, and B66, may be associated with lower respiratory tract infections and thus lead to higher hospitalization, increased morbidity, as well as lethality rates. The aim of this article is to synthesize and analyze the prevalence of specific HAdV types in pediatric patients worldwide. A systematic literature search was performed using MEDLINE, Scopus, and Web of Science. In total, n = 1167 titles and abstracts were screened, and 105 full-text articles were assessed for eligibility. Screening, data extraction, and appraisal were analyzed by reviewers, in accordance with PRISMA guidelines and JBI recommendations. We included studies reporting on currently circulating HAdV types (n = 16). Based on a systematic and narrative approach, relevant types of HAdV biology and infections in children are presented. In detail, HAdV-B3 and HAdV-B7 were commonly associated with severe respiratory tract infections, while HAdV-F40 and HAdV-F41 caused acute gastroenteritis. Moreover, detailed research revealed the critical role of HAdV-C2 and the necessity for particular attention to HAdVs in acute neurological infections. This comprehensive analysis highlights the significant global distribution and diverse clinical implications of different HAdV types in children, pointing out the need for continued surveillance to better understand HAdVs epidemiology and its implications for public health, and future preventive measures, in particular among vulnerable patients. Full article

Wastewater-based epidemiology (WBE) offers valuable insight into viral circulation at the community level. In this study, we combined digital PCR (dPCR) with molecular typing to investigate the prevalence and diversity of human adenoviruses (HAdVs) in untreated wastewater samples collected throughout Italy. HAdV genomes were detected in over 93% of the 168 samples analyzed, with concentrations up to 4.5 × 10⁶ genome copies per liter. For genotypic characterization, we used nested PCR followed by Sanger and Oxford Nanopore Technologies (ONTs) long-read sequencing. While Sanger sequencing identified three dominant genotypes (HAdV-A12, HAdV-B3, and HAdV-F41), ONT sequencing provided enhanced resolution, confirming all previously identified types and revealing seven additional genotypes: HAdV-B21, HAdV-C5, HAdV-D45, HAdV-D46, HAdV-D49, HAdV-D83, and HAdV-F40. This comprehensive approach highlights the added value of ONT long-read sequencing in uncovering the genetic complexity of adenoviruses in wastewater, particularly in detecting rare or low abundance types that conventional methods may miss. Our findings highlight the value of integrating quantitative and high-resolution molecular tools in WBE to improve surveillance and better understand the epidemiology of viral pathogens circulating in the human population. Full article

Adenoviral (AdV) vector-based vaccines employing the human AdV (HAdV) and chimpanzee AdV (ChAdV) vector platforms played a crucial role in combating the COVID-19 pandemic. However, the widespread use of these platforms, the prevalence of various HAdV types, and the resulting preexisting immunity have significantly impacted the vaccines utilizing these vector platforms. Considering these challenges, the bovine AdV type 3 (BAdV-3) vector system has emerged as a versatile and innovative platform for developing next-generation vaccines against infectious diseases. Inherent attributes like a high transduction efficiency, large transgene insertion capacity, broad tissue tropism, and robust induction of innate immunity add significant value to the BAdV vector platform for vaccine design. BAdV-3 vectors effectively elude HAdV-specific preexisting humoral and cellular immune responses. Additionally, BAdV-3 is low in pathogenicity for its host and is anticipated to be safe as a vaccine platform. This systematic review provides an overview of the development of BAdV-3 as a vaccine delivery platform and its application in designing vaccines for infectious agents of human and veterinary importance. Full article

Background and objectives: Acute gastroenteritis (AGE) remains a significant cause of morbidity in children, particularly in low- and middle-income countries. Viral pathogens, including rotavirus (RoV), norovirus (NoV), and adenovirus (HAdV), are among the leading causes of AGE. This study aimed to determine the prevalence of viral, bacterial, and parasitic enteric pathogens associated with AGE among hospitalized children in Northern Jordan. Materials and Methods: A total of 195 stool samples were collected from hospitalized children with AGE during the winter seasons of 2022–2024. Multiplex real-time qPCR assays were performed to detect common pathogens. The prevalence of each pathogen was determined, and co-infections were analyzed. Clinical symptoms, demographic characteristics, and associations between specific pathogens and disease severity were evaluated. Results: Viral pathogens were the predominant cause of AGE, with NoV detected in 53 cases (27.2%; of which 19.0% were NoV GI and 8.2% NoV GII), followed by RoV (24.1%), HAdV (20.0%), HAstV (13.3%), and SaV (12.3%). Co-infections were observed in several cases, particularly among viral infections evoked by RoV, HAdV, and NoV GI. Bacterial and parasitic infections were less prevalent, with Salmonella and Campylobacter spp. detected in 23.1% and 13.8%, respectively. Additionally, Cryptosporidium was identified in two cases (0.5%). Conclusions: Viral pathogens, particularly NoV, RoV, and HAdV, are the leading causes of AGE among hospitalized children in Jordan. Co-infections among viral pathogens were common, whereas bacterial and parasitic infections played a limited role in the disease burden. These findings emphasize the importance of continued surveillance and vaccination efforts, particularly for RoV, to reduce AGE-related hospitalizations in children. Full article

Human enteric adenoviruses (HAdV-F40/41) play a crucial role as causative agents of acute gastroenteritis (AGE), particularly affecting children in low-and middle-income countries. This study investigated the prevalence, genetic diversity, and molecular characteristics of HAdV-F40/41 in AGE cases reported in Brazil from 2021 to 2023, a period after the COVID-19 pandemic. A total of 1980 stool samples collected from medically attended AGE patients from nine states were analyzed by TaqMan-based qPCR. Overall, HAdV was detected in 16.6% (n = 328/1980) of cases, with the highest prevalence observed in children under five years of age. The positive HAdV samples were genotyped through partial sequencing of the hexon and/or fiber genes followed by phylogenetic analysis. Enteric HAdVs (HAdV-F40/41) were detected in 3.2% (n = 63/1980) of samples, with HAdV-F41 (44.1%) being the most common genotype. Among the non-enteric types, HAdV-C (29.4%) was the most prevalent, followed by HAdV-B (13.2%), HAdV-A (10.3%), and HAdV-D (2.9%). Phylogenetic analysis of the hexon (HVR1–HVR6) and fiber (Shaft) gene regions identified two major clusters, H-GTC1 and F-GTC2, showing close genetic relationships with global strains. HAdV-F40/41 demonstrated significantly higher viral loads compared to non-enteric HAdVs. These findings highlight the importance of continued surveillance of HAdV-F to better understand its role in AGE cases and support public health strategies, including potential vaccine development. Full article

Human adenovirus 36 (HAdV-36) is associated with obesity, potentially by promoting adipocyte proliferation and differentiation. Although linked to increased fat storage, HAdV-36 is also correlated with improved insulin sensitivity. Given its potential role in modulating adipose tissue and promoting a less inflammatory metabolic profile, its impacts on pro- and anti-inflammatory cytokine secretion remain unclear. Methods: This nested case-control study compared cytokine levels (IL-10, IL-2, IL-6, IL-8, and TNF-α) between patients with and without HAdV-36 infection. A total of 76 participants were included, with 37 in the control group (HAdV-36 negative) and 39 classified as cases (HAdV-36 positive). Results: HAdV-36 seropositive individuals exhibited significantly lower IL-6 levels and higher IL-8 levels than seronegative participants. Additionally, they had lower glucose levels, suggesting a potential link between HAdV-36 and metabolic regulation. Conclusions: These findings support the hypothesis that HAdV-36 may influence inflammatory and metabolic responses by modulating cytokine expression and glucose levels. Further research is needed to clarify the underlying mechanisms and their implications for metabolic health. Full article

Pneumonia and diarrhea are the leading causes of death in children under 5 globally, worsened by viral infections. This study investigates viral agents in children ≤ 3 years with respiratory illness and diarrhea in Metropolitan Region of São Paulo, Brazil, during spring 2021. Twenty paired samples (oropharyngeal swab and feces) were tested using in-house qPCR for HBoV and HAdV, RT-qPCR for RVA, EV, PeV-A, and NoV, and a commercial RT-qPCR kit for SARS-CoV-2, Flu A/B, and RSV. HAstV was detected with conventional nested (RT)-PCR. Positive samples were sequenced for molecular characterization and phylogenetic analysis. Seven viruses were identified: HBoV, NoV, HAdV, PeV-A, EV, RSV, and Flu A. HBoV and NoV were detected in 75% of cases, with co-infection in 65% of patients, indicating their involvement in the gastro-respiratory illness. Genotyping of HBoV (HBoV-1), NoV (GII.4_Sydney[P16], GII.2[P16], and GII.4_Sydney[P31]), EV (Coxsackievirus A6), HAdV (species C, type 6), and PeV-A (genotype 1) showed local virus diversity. Phylogenetic analysis indicated no ongoing community outbreak, with distinct clusters observed. The findings highlight the overlap of respiratory and enteric diseases, revealing local viral diversity and high exposure to enteric viruses. This underscores the challenges in differential diagnosis and the need for syndromic surveillance. Full article

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies. Full article

Background: The etiology of obesity has been associated with genetic and epigenetic factors, hormonal changes, unhealthy lifestyle habits, and infectious agents such as human adenovirus-36 (HAdV-36). Viral infections induce reactive oxygen species, and the imbalance between oxidative stress/antioxidant results in fat accumulation. In the Mexican population, little is known about the frequency of HAdV-36 and its effect on the balance between antioxidants and oxidants, inflammation, and metabolic markers. The purpose of our study was to evaluate the frequency of HAdV-36 seroprevalence and its relation to body mass index (BMI), lipid profiles, glucose levels, inflammation, and levels of antioxidants and oxidative stress in a representative sample. A cross-sectional study was carried out on 112 healthy adults between 18 and 28 years old, who were divided into four groups according to their BMI: underweight (BMI < 18.5); normal weight (BMI 18.5–24.9); overweight (BMI ≥ 25); and obese (BMI ≥ 30). Blood samples were taken to evaluate lipid and glucose profiles, as well as antioxidant and oxidative stress status, using colorimetric techniques. Seropositivity for HAdV-36 and levels of TNF-α, IL-6, and cortisol were determined using an enzyme-linked immunosorbent assay. The HAdV-36 frequency was 15.6% in underweight subjects, 18.7% in the normal-weight subjects, 34.37% in the overweight subjects, and 31.24% in the obese subjects. The subjects who were positive for HAdV-36 seroprevalence had increased levels of IL-6, cortisol, and oxidative stress, independently of BMI. The HAdV-36-positive subjects had reduced LDL-C and HDL-C levels only in the low-weight groups. Glutathione and SOD levels increased in the underweight and normal-weight subjects with positive HAdV-36 seroprevalence, while catalase levels decreased in the normal-weight, overweight, and obese subjects. In conclusion, for the first time, an HAdV-36 seroprevalence in the adult Mexican population is reported which was higher and had a relation with the presence of inflammation, alterations in the lipid profile, and imbalance between oxidative stress and antioxidant status, regardless of BMI. The oxidative stress/antioxidant imbalance could be participating in the stimulation of white adipose tissue deposition. Full article

The abundant production of foreign proteins and nucleic acids during viral infection elicits a variety of stress responses in host cells. Viral proteins that accumulate in the endoplasmic reticulum (ER) can trigger the unfolded protein response (UPR), a coordinated signaling program that culminates in the expression of downstream genes that collectively restore protein homeostasis. The model pathogen adenovirus serotype 5 (HAdV5) activates the UPR via the signaling axis formed by inositol-requiring enzyme type 1 (IRE1α) and the X-box binding protein 1 (XBP1), a transcription factor required for immune function. Recent studies have suggested that IRE1α-XBP1 activity supports adenovirus replication. Here, we show that HAdV5 exerted opposing effects on IRE1α and XBP1. IRE1α was activated in response to HAdV5, but the production of the XBP1 isoform, XBP1s, was post-transcriptionally blocked. The tumor suppressor p53, which is eliminated by HAdV5 after infection, inhibited IRE1α activation. The de-repression of IRE1α following the degradation of p53 conceivably reflects a novel antiviral mechanism, which HAdV5 ultimately evades by co-opting IRE1α and suppressing XBP1s. Our findings illustrate the opposing mechanisms used by adenoviruses and their host cells to exert control over the UPR, a critical determinant of cell fate. Full article