Search Results (157)

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

Human adenoviruses (HAdVs) are known to be highly contagious pathogens. They are commonly associated with mild respiratory infections in young children but can also cause severe life-threatening infections. Human adenovirus types 4 and 7 have frequently been reported to cause pneumonia in immunocompetent youths and adults. In this retrospective study, we analyzed the clinical, laboratory, radiological, and microbiological features, as well as the treatment and outcomes of an adenovirus outbreak in 185 patients who were admitted to the Emergency Unit of the Departments of Infectious Diseases and Pediatrics, University Hospital of Split, Croatia, between October 2022 and April 2023. An unusual increase in the frequency of adenovirus pneumonia was observed, especially in adults, followed by respiratory failure and complications such as pulmonary embolism. The most common chest X-ray findings were unilateral patchy opacity and unilateral reticulations (11.6%), followed by unilateral lobar pneumonia (7.1%). The predominant CT presentation was unilateral lobar pneumonia with multiple patchy ground glass opacities (23.5%) or lobar pneumonia with mixed opacities (17.6%). We found a low correlation between Brixia score and C-reactive protein in adults and no correlation in children. Adenovirus type 7 was almost exclusively isolated from patients with pneumonia. Most of our patients with severe or critical adenovirus pneumonia were immunocompetent adults without any medical history. So far, only a few studies have presented the radiological features of HAdV pneumonia, which generally did not reveal lobar pneumonia in a substantial percentage. Our research also demonstrated an unusual presentation of adenovirus infection complicated with pulmonary embolism, which has rarely been reported in previous studies. The aforementioned HAdV outbreak indicates the necessity for further research, especially in the context of effective antiviral therapy and infection prevention. Full article

Adenovirus (AdV) infection has been rarely documented in cats and other felids. Partial sequences of the hexon and fiber genes of a Hungarian feline adenovirus isolate (FeAdV isolate) showed a close relationship to human AdV (HAdV) type C1. Further molecular and biological characterization is reported here. Whole-genome sequencing revealed two silent mutations in the genome of the FeAdV isolate compared to a HAdV-C1 reference strain (at positions 14,096 and 15,082). Competitive antibody binding to the Coxsackie–adenovirus receptor and α_vβ₃ and α_vβ₅ integrin coreceptors inhibited the binding of the FeAdV isolate in different cell lines, but residual infections suggested alternative entry routes. The FeAdV isolate was found to be more sensitive to heat, low pH and detergents, but more resistant to alkaline and free chlorine treatments, as well as to ribavirin, stavudine and cidofovir treatments, than other human AdV types. We observed a suppression of IL-10 and TGF-β1 production during the entire course of viral replication. This immunomodulation may restore intratumoral immunity; thus, the FeAdV isolate could serve as an alternative oncolytic vector. Collectively, our results support that the Hungarian FeAdV isolate is a variant of common HAdV-C1. The cohabitation of cats with humans might result in reverse zoonotic infection. Felids appear to be susceptible to persistent and productive adenovirus infection, but further studies are needed to better understand the clinical and epidemiological implications. Full article

Human adenovirus (HAdV)-based oncolytic vectors, which are designed to preferentially replicate in and kill cancer cells, have shown modest efficacy in human clinical trials in part due to poor viral distribution throughout the tumor mass. Previously, we showed that expression of the p14 fusion-associated small transmembrane (FAST) fusogenic protein could enhance oncolytic HAdV efficacy and reduce tumor growth rate in a human xenograft mouse model of cancer. We now explore whether co-expression of the adenovirus death protein (ADP) with p14 FAST protein could synergize to further enhance oncolytic vector efficacy. ADP is naturally encoded within the early region 3 (E3) of HAdV, a region which is frequently removed from HAdV-based vectors, and functions to enhance cell lysis and progeny release. We evaluated a variety of approaches to achieve optimal expression of the two proteins, the most efficient method being insertion of an expression cassette within the E3 deletion, consisting of the coding sequences for p14 FAST protein and ADP separated by a self-cleaving peptide derived from the porcine teschovirus-1 (P2A). However, the quantities of p14 FAST protein and ADP produced from this vector were reduced approximately 10-fold compared to a similar vector-expressing only p14 FAST protein and wildtype HAdV, respectively. Compared to our original oncolytic vector-expressing p14 FAST protein alone, reduced expression of p14 FAST protein and ADP from the P2A construct reduced cell-cell fusion, vector spread, and cell-killing activity in human A549 adenocarcinoma cells in culture. These studies show that a self-cleaving peptide can be used to express two different transgenes in an armed oncolytic HAdV vector, but also highlight the challenges in maintaining adequate transgene expression when modifying vector design. Full article

Respiratory viruses are among the most common causes of human infections. Examining pathological processes linked to respiratory viral infections is essential for diagnosis, treatment strategies, and developing novel therapeutics. Alterations in oxidative stress levels and homeostasis are significant processes associated with respiratory viral infections. The study aimed to compare selected oxidative stress markers: total oxidative status (TOS), total antioxidant capacity (TAC), and the oxidative stress index (OSI) levels and glutathione peroxidase (GPx) and glutathione reductase (GR) activities in normal (MRC5 cell line) and tumor (A549 cell line) lung cells infected with human coronaviruses (HCoV) OC43 and 229E, human adenovirus type 5 (HAdV5), or human rhinovirus A (HRV A). We observed that a respiratory viral infection more significantly affected non-enzymatic oxidative stress markers in a lung adenocarcinoma model (A549 cells), while human lung fibroblasts (MRC-5 cell line) presented changes in enzymatic and non-enzymatic oxidative stress markers. We suggest that further detailed research is required to analyze this phenomenon. Full article