Human Adenovirus Research Articles

A humanized neutralizing antibody protects against human adenovirus type 7 infection in humanized desmoglein-2 and CD46 double-receptor transgenic mice.

Human adenovirus type 7 (HAdV7) has become a major public health threat due to its widespread transmission, severe associated pneumonia, and a lack of effective anti-HAdV7 drugs. The aim of the current study is to design a humanized monoclonal antibody (mAb) demonstrating efficacy against HAdV-7 infections in vitro and in vivo. The humanized neutralizing antibody, 3G5-hu, was derived from the murine mAb 3G5. Antibody activity was evaluated using a flow cytometry-based neutralization (FCN) assay to identify humanized mAbs retaining potent neutralizing activity. Additionally, a humanized hDSG2/hCD46 dual-receptor transgenic mouse model was developed to simulate HAdV-7 infection. Using recombinant HAdV-7 expressing enhanced green fluorescent protein and clinically isolated wild-type HAdV-7, the half-maximal effective concentration of 3G5-hu against HAdV-7 was determined to be < 30 ng/mL. Notably, 3G5-hu exhibits high specificity for the hexon protein of the HAdV-7 capsid (affinity: KD = 9.02 × 10- 11 M). Microneutralization studies with wild-type HAdV-7 and rAd7EGFP confirmed that humanized mAb 3G5-hu neutralizes 10-30 ng/mL HAdV-7 (approximately 67-200 pM). Furthermore, hDSG2/hCD46 double-receptor transgenic mice are more susceptible to HAdV-7 infection than single-receptor transgenic mice. Meanwhile, the humanized mAb 3G5-hu provides good protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice. The newly designed humanized mAb 3G5-hu specifically neutralizes HAdV-7 in vitro and in vivo. 3G5-hu elicits protection against HAdV-7 infection in hDSG2/hCD46 knock-in transgenic mice. The findings of this study provide insights to guide the future development of preventative and therapeutic treatments for HAdV-7 infection.

Diels–Alder Adducts of &lt;i&gt;N&lt;/i&gt;-Substituted 2-Pyridones with Maleinimides. Synthesis and Antiviral Activity

Adducts of N-substituted 2-pyridones [pyridine-2(1H)-ones] and N-substituted maleic acid imides were synthesized under thermal conditions of the Diels–Alder reaction with yields from 68 to 97%. Cytotoxicity and antiviral activity of the obtained compounds were studied using a model of adenovirus infection [human adenovirus type 5 (AdV5)] in MA-104 cell culture. It was shown that the synthesized adducts have low toxicity and medium antiviral activity. Only 9-hexyl-2-phenyl-3a,4,7,7a-tetrahydro-1H-4,7-(epiminomethano)isoindole-1,3,8-trione has the most pronounced viral inhibitory properties with a selectivity index of 7.

Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.

The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads. Similar to FX, the γ-carboxyglutamic acid (Gla) domain of FII binds within the surface cavity of hexon trimers. While FII binds equally to species-C Ads: Ad5, Ad6, and Ad657, FX exhibits significantly better binding to Ad5 and Ad657 compared to Ad6. Although only the FX-Gla domain is observed at high-resolution (3.7 Å), the entire FX is visible at low-resolution bound to Ad5 in three equivalent binding modes consistent with the 3-fold symmetric hexon. Only the Gla and kringle-1 domains of FII are visible on all the species-C adenoviruses, where the rigid FII binds in an upright fashion, in contrast to the flexible and bent FX. These data suggest that differential binding of FII and FX may shield certain species-C adenoviruses differently against immune molecules, thereby modulating their tropism.

The Effects of Different Respiratory Viruses on the Oxidative Stress Marker Levels in an In Vitro Model: A Pilot Study

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.

Reverse resistance to immune checkpoint inhibitor in a patient with recurrent cardia cancer by intratumoral injection of recombinant human adenovirus type 5: a case report and literature review

Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Longitudinal Analysis of Binding Antibody Levels Against 39 Human Adenovirus Types in Sera from 60 Regular Blood Donors from Greifswald, Germany, over 5 Years from 2018 to 2022

Adenoviruses are important human pathogens that are widespread and mainly associated with respiratory and gastrointestinal infections. In a previous study on human adenovirus (HAdV) seroprevalence, we observed reduced binding antibody levels against a range of HAdV types in sera collected from students in 2021 compared to sera collected before the SARS-CoV-2 pandemic. In this follow-up study, we wanted to verify this observation in a cohort of regular blood donors for whom serial samples were available. Therefore, HAdV-specific binding antibody levels were analyzed in sera collected over a 5-year period from 2018 to 2022 in a cohort of 60 regular donors to the blood bank of the University Hospital in Greifswald, Germany. Using ELISA-based assays, we quantified the binding antibody responses against 39 HAdV types. On the cohort level, we found largely stable antibody levels over the analyzed time period, with the highest antibody responses against HAdV-C1, -D25, -D26, -E4, -D10, -D27, -C5, -D75, -C2, and -C6. Only minor but significant reductions in comparison to the first serum samples from 2018 were detected for antibody levels in 2021 and 2022 against the low-prevalent types HAdV-A31, -D8, -D20, -D37, -D65, and -D69. On the other hand, we detected fluctuations in antibody levels on the individual level, with strong increases in antibody levels indicative of novel antigen contact. Interestingly, we frequently found simultaneous changes in antibody responses against multiple HAdV types, resulting in strong correlations of antibody responses against distinct clusters of HAdVs suggesting extensive cross-reactivity of HAdV-specific antibodies. To our knowledge, this is the first study of antibodies against a broad range of HAdV types in serum samples collected from a cohort of individuals over a prolonged period, and our data provide important insight into the long-term stability of HAdV-specific antibody levels. In this cohort of regular blood donors, we did not observe any major impact of the SARS-CoV-2 pandemic on HAdV immunity. Correlations of changes in antibody levels against different types indicate cross-reactivity of HAdV-specific antibodies that are important to consider for HAdV vector development. Our data also reveal possible candidates for future development of HAdV-based vectors.

Protective efficacy of a recombinant adenovirus expressing novel dual F and HN proteins of bovine parainfluenza virus type 3

Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection.

Epidemiology of Acute Infectious Diarrhea-Associated Viruses in Children in Hangzhou, China, 2023

Abstract Objective To investigate the epidemiological characteristics of children infected with diarrheal virus in Hangzhou, China, 2023. Methods From January 2023 to December 2023, 20,939 stool samples from children with acute infectious diarrhea were collected for the detection of rotavirus A and human adenovirus (HAdV), using latex agglutination detection kits; 7,584 stool samples were collected for the detection of norovirus, using real-time polymerase chain reaction reagent. Results A total of 639 (3.0%, 639/20,939) tested positive for rotavirus A, and 1,201 (5.7%, 1,201/20,939) positive samples were detected by colloidal gold method. The positive rates of norovirus were 42.2% (3,203/7,585). Among all age groups, the rotavirus A positive detection rate was the highest in participants aged 3 to 6 years (6.46%, 260/4,024). The monthly distribution of patients with rotavirus A showed that the number of cases was the lowest in October (0.45%, 8/1,779) and reached the peak in April (7.97%, 144/1,806). The highest and lowest positive rates among all age groups for HAdV were found in children aged 3 to 6 years(8.27%, 333/4,024) and in those aged 0 to 6 months (2.21%, 60/2,717). The monthly positivity rates of HAdV spanning from January to November 2023 were 1.38, 1.44, 2.34, 3.65, 6.64, 7.71, 7.54, 7.13, 6.82, 4.15, and 6.50%, and reached the peak in December (8.17%). For norovirus, children aged 1 to 3 years had the highest positive detection rate (57.95%, 1,349/2,328), while infants aged 0 to 6 months had the lowest positive detection rate (19.60%, 205/1,046). The results show that January had the lowest number of cases (14.63%, 6/41), while September had the highest (50.51%, 545/1,079). Conclusion The detection rate of rotavirus A and HAdV was highest among participants aged 3 to 6 years, whereas the detection rate of norovirus was highest among those aged 1 to 3 years. The monthly distribution peaks for the three enteric viruses varied significantly.

Metabolomic profiling reveals new insights into human adenovirus type 7 infection

Human adenovirus type 7 (HAdV-7) is a prominent pathogen that causes severe pneumonia in children in China. However, the interaction between HAdV-7 infection and host metabolism is still poorly understood. To gain a comprehensive understanding of the metabolic interplay between host cells and the virus, we analysed the energy and lipid metabolism profiles of the HAdV-7-infected lung cancer cell line A549 by ultrahigh-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (ESI-QTRAP-MS/MS). Our study revealed significant alterations in various metabolic processes, including the tricarboxylic acid cycle, purine and pyrimidine metabolism, amino acid metabolism, nucleotide metabolism, and lipid metabolism, in A549 cells after HAdV-7 infection. Moreover, HAdV-7 infection stimulated enhanced synthesis of membrane lipids in A549 cells. These findings emphasize the crucial role of metabolism in viral infection and suggest that modulating host cell metabolism could be a promising approach for targeted drug development and infection control.

An in silico approach uncovering the competency of oncolytic human adenovirus 52 for targeted breast cancer virotherapy

Breast cancer remains a major health threat throughout the world specifically in women above 30 years of age however, it is rarely known to affect men as well. It is characterized by the abnormal division of cells in the breast tissue resulting in the development of breast malignancies. Various risk factors contributing to breast cancer include age, family history, genetic mutations (chiefly in BRCA1 and BRCA2 genes) along with hormonal imbalances (oestrogen, progesterone, HER2). Early detection which can be obtained through frequent rounds of self-examination, mammographic scanning, and clinical assessment plays a crucial role in the prevention of the disease. In addition, appropriate diagnosis assists in better therapeutic responses. This study highlights the considerable health risks associated with the conventional treatment procedures which arise and increased demand of advanced, secure, and risk-free treatment alternatives. Oncolytic viruses are potentially apparent for the aim of improving cancer therapeutics with reduced side effects. These viruses act as the fundamental therapeutic agent themselves that selectively target and kill malignant cells without harm to healthy tissues. The key objective of the research is to provide evidence that Human Adenovirus 52 is a potent oncolytic virus and to highlight its capacity to target and eliminate cancer cells with precision while causing the least amount of harm to healthy tissues. Validating the in-silico method entails evaluating the precision and dependability of the computational modelling by contrasting the in-silico predictions with the findings from the experiments rank as the secondary objective. The workflow of this research utilized in-silico computational drug designing approaches including retrieval of tertiary structures of both the target Breast Cancer Type 1 Susceptibility Protein (BRCA1) and the viral Human Adenovirus 52 protein, their validation generating Ramachandran Plots determining favoured amino acid residue angles and prediction of their active residues. Furthermore, the study focused on the molecular dynamics docking of proteins, interpretation of molecular interactions between the docked complex, as well as the assessment of the molecular dynamic simulations (MD) in addition to their MMGBSA binding energy calculations. A successful docking between BRCA1 and Adenovirus protein provided a significant score of 329.2 +/- 24.3, furthermore, MD simulations showed a high RMSD peak at 2.8 Å, RMSF were maximum at 3.5 Å with highest protein–protein interaction, the radius of gyration was stable throughout the simulation representing elastic stability along with a high energy interaction value of - 7882 kCal/mol. Moreover, the MMGBSA calculation results showed a notable release of binding free energy of - 68.96 kCal/mol demonstrating effective bond formation between the docked complex. These findings propose the effectiveness of Human Adenovirus 52 to treat cancer. The selected oncolytic Human Adenovirus 52 is a potential candidate for the target specific treatment of breast cancer through virotherapy. This computer-aided drug discovery presents significant potential in targeting cancer cells and would assist in the development of potent drug reagents for the cancer therapy.

Evaluation of Immunochromatographic Test for Rapid Detection of Norovirus, Rotavirus, and Adenovirus in Stool Samples.

Viral enteric infections are illnesses caused by several types of viruses that primarily affect the gastrointestinal system. Globally, three major viruses associated with gastroenteritis, including norovirus (NoV), rotavirus A (RVA), and human adenovirus (HAdV), have been widely recognized. Accordingly, a rapid and sensitive diagnostic tool, such as immunochromatographic (IC) test, for diarrheal virus detection is required and helpful for rapid diagnosis. The IP-Triple I IC test kit for simultaneous triple virus detections of NoV, RVA, and HAdV was evaluated for its efficacy by using stool specimens that were known positive for these viruses by real-time RT-PCR or PCR, which was used as the gold standard method. The results revealed that the IP-Triple I IC test kit exhibited a very high level of specificity (100%) for NoV, RVA, and HAdV detections, while the sensitivity was slightly different for these three viruses. The sensitivity of detection for RVA was 86.7%, whereas those for NoV and HAdV were 70.6% and 76.2%, respectively. This IP-Triple I IC kit could detect common antigens of a wide range of NoV, RVA, and HAdV genotypes (NoV GII.2, GII.4, GII.6, GII.7, GII.10, GII.17, RVA G1P[8], G2P[4], G3P[8], G8P[8], G9P[8], HAdV-C1, -C2, -C5, -A12, -F40, and -F41). Our results revealed that the IP-Triple I IC test kit is highly effective for simultaneous, direct detection of common antigens of several genotypes of NoV, RVA, and HAdV in stool specimens and useful for screening and rapid diagnosis of diarrheal viruses during the seasonal outbreak.

Construction and validation of a mouse model for studying severe human adenovirus infections

Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to mortality, especially in immunosuppressed patients, young children, and military recruits. Currently, no vaccines or specific drugs are approved for clinical use. The hosts of adenoviruses are strictly species-specific, which strongly limits the development of vaccines and drugs against HAdVs. In this study, immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5 (HAdV-5) via tail intravenous injection (i.v.). All mice challenged with a high dose of HAdV-5 (3.2×1010 TCID50/kg) died within 3 to 5 days, while those receiving a low dose of HAdV-5 (8×109 or 4×109 TCID50/kg) survived. Interestingly, among the mice receiving a medium dose of HAdV-5 (1.6×1010 TCID50/kg), 60% (n = 3/5) of male mice died, while all female mice survived. This suggests that male mice may be more susceptible to HAdV-5 infection than female mice, consistent with clinical findings in children. HAdV-5 DNA was mainly distributed in the liver, followed by the spleen and lungs. Pathological changes were observed in the lungs, liver, and spleen, with severity increasing in correlation with the virus challenge dosage. Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the H2-Aa, H2-Ea-ps, CD74, and H2-Eb1 genes in male mice, as well as the AHR gene in female mice, may contribute to the observed higher mortality rates in male mice. Therefore, this effective, feasible, and cost-efficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.

Cyclodextrin-based iodophors with high iodine retention in solid state and in dilute solutions

Iodine is a broad-spectrum antiseptic with the advantage of not inducing bacterial resistance, but its use is limited by volatility. This issue can be overcome by using “iodophors”, which are molecular systems able to retain iodine and provide its sustained release. Cyclodextrins have proven effective in stabilizing iodine in solution through the formation of complexes, the preparation of which in solid form could offer additional benefits in terms of handling and storage. A series of cyclodextrins (CD) were tested for their ability to form solid complexes with iodine and it was found that the addition of potassium iodide in the solid-state preparation of the complexes significantly increases both iodine incorporation and long-term stability compared to the solids obtained without added potassium iodide. Dilute aqueous solutions of the obtained complexes were monitored for their iodine content in different conditions and excellent stability was observed in some cases. Furthermore, these cyclodextrin‑iodine complexes showed no cytotoxic effects on human corneal epithelial cells (HCE-2) while displayed very high antimicrobial (against Staphylococcus epidermis) and antiviral (against Human adenovirus 5) activities. These findings highlight the potential of cyclodextrins as a versatile platform for the development of solid iodophors as an alternative to the traditional povidone-iodide formulation.

A newly identified secretory phospholipase A2 group XIIA homolog (LcPLA2XIIA) in Larimichthys crocea exhibits antimicrobial and antitumor activities

The phospholipase A2 (PLA2) superfamily has attracted increasing attention in recent years due to the multiple physiological and pathological functions exerted by its members. Up to date, the knowledge about the biological role of PLA2XIIA subfamily members remains limited. In this study, a new member of PLA2XIIA subfamily, LcPLA2XIIA, was characterized in large yellow croaker. Different from most members of the PLA2 superfamily with positive charge, LcPLA2XIIA encodes an anionic protein, which is similar to other members of PLA2XIIA subfamily. LcPLA2XIIA is highly expressed in the intestine, and afterwards, it is up-regulated after with Pseudomonas plecoglossicida or Staphylococcus aureus. LcPLA2XIIA exhibits strong inhibitory activity against these two bacteria. The results indicate that LcPLA2XIIA plays an important role in the antimicrobial immune responses of large yellow croaker. LcPLA2XIIA displays strong binding activity to all the tested bacteria. It specifically interacts with LTA, a unique component on the surface of Gram-positive bacteria. It also significantly promotes bacterial agglutination in the presence of Ca2+. These findings reveal that the binding and agglutinating abilities of LcPLA2XIIA to bacteria contribute greatly to its antibacterial activity. In addition, LcPLA2XIIA significantly inhibits the proliferation of infectious hematopoietic necrosis virus instead of recombinant human adenovirus type 5. It also suppresses the growth of human colorectal adenocarcinoma cells by inducing apoptosis, but it has no obvious inhibitory effect on the growth of epithelioma papulosum cyprinid cells. This study provides new insights into the antibacterial activity, and the mechanism of LcPLA2XIIA in large yellow croaker, and antiviral and antitumor functions of PLA2XIIA subfamily members.

Uncovering the Potent Antiviral Activity of the Sesterterpenoids from the Sponge Ircinia Felix Against Human Adenoviruses: from the Natural Source to the Total Synthesis.

Human Adenovirus (HAdV) infections in immunocompromised patients can result in disseminated diseases with high morbidity and mortality rates due to the absence of available treatments for these infections. The sponge Ircinia felix was selected for the significant anti-HAdV activity displayed by its organic extracts. Its chemical analysis yielded three novel sesterterpene lactams, ircinialactams J-L, along with three known sesterterpene furans which structures were established by a deep spectrometric analysis. Ircinialactam J displayed significant antiviral activity against HAdV without significant cytotoxicity, showing an effectiveness 11 times greater than that of the standard treatment, cidofovir®. Comparison of the antiviral evaluation results of the isolated compounds allowed us to deduce some structure-activity relationships. Mechanistic assays suggest that ircinialactam J targets an early step of the HAdV replicative cycle before HAdV genome reaches the nucleus of the host cell. The first total synthesis of ircinialactam J was also accomplished to prove the structure and to provide access to analogues. Key steps are a regio- and stereoselective construction of the trisubstituted Z-olefin at Δ7 by iron-catalyzed carbometallation of a homopropargylic alcohol, a stereoselective methylation to generate the stereogenic center at C18, and the formation of the (Z)-Δ20 by stereoselective aldol condensation to introduce the tetronic acid unit. Ircinialactam J is a promising chemical lead to new potent antiviral drugs against HAdV infections.

Contribution of Other Respiratory Viruses During Influenza Epidemic Activity in Catalonia, Spain, 2008–2020

Background: During seasonal influenza activity, circulation of other respiratory viruses (ORVs) may contribute to the increased disease burden that is attributed to influenza without laboratory confirmation. The objective of this study was to characterize and evaluate the magnitude of this contribution over 12 seasons of influenza using the Acute Respiratory Infection Sentinel Surveillance system in Catalonia (PIDIRAC). Methods: A retrospective descriptive study of isolations from respiratory samples obtained by the sentinel surveillance network of physicians was carried out from 2008 to 2020 in Catalonia, Spain. Information was collected on demographic variables (age, sex), influenza vaccination status, epidemic activity weeks each season, and influenza laboratory confirmation. Results: A total of 12,690 samples were collected, with 46% (5831) collected during peak influenza seasonal epidemic activity. In total, 49.6% of the sampled participants were male and 51.1% were aged &lt;15 years. Of these, 73.7% (4298) of samples were positive for at least one respiratory virus; 79.7% (3425 samples) were positive for the influenza virus (IV), with 3067 samples positive for one IV type, 8 samples showing coinfection with two types of IV, and 350 showing coinfection of IV with more than one virus. The distribution of influenza viruses was 64.2% IVA, 35.2% IVB, and 0.1% IVC. Of the other respiratory viruses identified, there was a high proportion of human rhinovirus (32.3%), followed by human adenovirus (24.3%) and respiratory syncytial virus (18; 7%). Four percent were coinfected with two or more viruses other than influenza. The distribution of coinfections with ORVs and influenza by age groups presents a significant difference in proportions for 0–4, 5–14, 15–64 and &gt;64 (21.5%, 10.8%, 8.2% and 7.6%: p &lt; 0.001). A lower ORVs coinfection ratio was observed in the influenza-vaccinated population (11.9% vs. 17.4% OR: 0.64 IC 95% 0.36–1.14). Conclusions: During the weeks of seasonal influenza epidemic activity, other respiratory viruses contribute substantially, either individually or through the coinfection of two or more viruses, to the morbidity attributed to influenza viruses as influenza-like illness (ILI). The contribution of these viruses is especially significant in the pediatric and elderly population. Identifying the epidemiology of most clinically relevant respiratory viruses will aid the development of models of infection and allow for the development of targeted treatments, particularly for populations most vulnerable to respiratory viruses-induced diseases.

Emerging zooanthroponotic risks: Detection of the human norovirus GII.4 Sydney[P31] strain in a domestic dog in Brazil

Recent increases in zoonotic diseases underscore the integration of companion animals into urban environments, posing complex transmission risks and highlighting the necessity of One Health approaches. Respiratory and enteric viruses have been consistently linked to interspecies transmission between humans and animals. This study aimed to assess the circulation of human noroviruses (NoV), human adenoviruses (HAdV), enteroviruses (EV), parechoviruses (PeV-A), human bocaviruses (HBoV), hepatitis A (HAV) and E viruses (HEV), Influenza A and B viruses (Flu A/B), respiratory syncytial virus (RSV), and SARS-CoV-2 in domestic dogs and cats in Brazil to understand potential zooanthroponosis risks. Between 2012 and 2021, 600 fecal samples from dogs and cats (516 and 84, respectively) were collected at small animal clinics in São Paulo state, Brazil. The specimens underwent in-house qPCR screening for HBoV and HAdV, while EV, PeV-A, NoV, and HEV were tested using in-house RT-qPCR. SARS-CoV-2, Flu A/B, and RSV were investigated with a commercial RT-qPCR kit assay. HAV detection utilized conventional nested (RT)-PCR. Positive samples were sequenced for molecular characterization and phylogenetic analysis. NoV was detected in 0.2 % (1/600) of the animals, while all other investigated viruses tested negative. The NoV-positive sample, collected in 2012 from a pet dog, was identified as genotype GII.4_Sydney[P31]. The Dog/BRA/2012/GII.4_Sydney[P31]/IAL-M21 strain exhibited a close genetic relationship to Brazilian human and environmental NoV GII.4_Sydney[P31] strains, with 98.1–99.2 % nucleotide similarity in ORF1 and 99.2–99.6 % in ORF2 sequences, suggesting interspecies transmission. Pet dogs are frequently exposed to human fecal-borne viruses, highlighting the potential for zooanthroponotic transmission due to their close interaction with humans in shared environments. There is an urgent need to enhance surveillance studies in companion animals to better understand the implications of detecting human NoV strains in pets, as NoV could potentially act as a reverse zoonotic disease in households, animal hospitals, or shelters worldwide.

The circulating characteristics of common respiratory pathogens in Ningbo, China, both before and following the cessation of COVID-19 containment measures

To assess the circulating characteristics of common respiratory pathogens following the complete relaxation of non-pharmaceutical interventions (NPIs) and the cessation of the dynamic zero-COVID policy. The retrospective analysis was conducted from 14,412 patients with acute respiratory infections (ARIs) from January 24, 2020, to December 31, 2023, including Influenza A virus (IFV-A), Influenza B virus (IFV-B), Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV), Human Parainfluenza Virus (HPIV), Human Metapneumovirus (HMPV), Human Coronavirus (HCoV), Human Bocavirus (HBoV), Human Adenovirus (HAdV), and Mycoplasma pneumoniae (MP). Compared with 2020–2022, Joinpoint analysis indicated a monthly increase in overall pathogen activity in 2023, rising from an average of 43.05% to an average of 68.46%. The positive rates of IFV-A, IFV-B, HMPV, HPIV, HCoV, and MP increased, while those of HRV and RSV decreased, and no differences in HAdV and HBoV. The outbreak of IFV-A and MP was observed, the positive rate of MP has surpassed pre-COVID-19 pandemic levels and the spread of RSV was interrupted by IFV-A. Infants and toddlers were primarily infected by HRV and RSV, Children and adolescents exhibited a higher prevalence of infections with MP, IFV-A, and HRV, whereas Adults and the elderly were primarily infected by IFV-A. The incidence of co-infections rose from 4.25 to 13.73%. Restricted cubic spline models showed that the susceptible age ranges for multiple pathogens expanded. These changes serve as a reminder to stay alert in the future and offer clinicians a useful guide for diagnosing and treating.

Adenovirus-5 and adenovirus-37 seropositivity in obese patients.

Obesity is a major health issue linked to conditions like diabetes, hypertension, and hyperlipidemia. Infectobesity suggests that certain microorganisms may contribute to obesity. Human adenovirus serotypes, particularly Human adenovirus type-36 (HAdV-36), Human adenovirus type-5 (HAdV-5), and Human adenovirus type-37 (HAdV-37), are thought to influence body fat regulation. This study investigates the relationship between Immunoglobulin G (IgG) positivity for HAdV-5 and HAdV-37 and obesity, aiming to provide data on the infectious etiology of obesity. Blood samples separated into serums from obese (BMI ≥30) and non-obese (BMI 18.5-25) individuals were tested for HAdV-5 and HAdV-37 seropositivity using ELISA kits and seropositivity rates between the groups were compared. HAdV-37 antibody positivity was significantly higher in obese patients (39/48) compared to the control group (24/42) (p=0.011). For HAdV-5, antibody positivity was similar in both groups (26 individuals each) with no significant difference (p=0.461). No significant gender-related differences were found for either serotype. The study suggests HAdV-37 may be associated with obesity, while no such relationship was found for HAdV-5. There was no gender association for either serotype. These results align with existing literature on HAdV-37, but further research is needed to confirm the link between adenoviruses and obesity and explore potential treatment options.

Epidemiological and pathological characterization of acute respiratory infections.

This research comprehensively investigates the epidemiological features and pathogen profile of acute respiratory infections (ARI) in Shihezi City, Xinjiang. A pivotal aspect of this study is the construction of a Bayes discriminant function for principal pathogen infections. This innovative methodology aims to furnish a robust scientific basis for the prevention and clinical management of ARI, potentially guiding more effective strategies in both public health and clinical settings. We compiled and examined data from January 2020 to June 2023, pertaining to patients admitted with acute respiratory infections at the First Affiliated Hospital of Shihezi University. This investigation focused on discerning patterns in epidemiology and pathogen etiology. Among 2110 cases of acute respiratory infections (ARI), 1736 underwent pathogenetic testing. Of these, 595 cases tested positive for at least one pathogen, marking a positivity rate of 34.27%. Viral detections, at a rate of 27.47%, were notably higher than bacterial detections, which stood at 6.51%. The most prevalent viruses identified were Human respiratory syncytial virus (hRSV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and Human adenovirus (HAdV), while the dominant bacterial pathogens included Klebsiella pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Co-infections were observed in 76 cases, accounting for 12.77% of positive diagnoses, predominantly involving hRSV in conjunction with other pathogens. In cases of acute bronchiolitis, hRSV was the most frequent pathogen, contributing to 23.10% of such cases. Similarly, in severe pneumonia cases, SARS-CoV-2 was predominant, accounting for 25.4% of these infections. The group with bacterial positivity exhibited elevated levels of C-reactive protein (CRP, 19.17 mg/L) and neutrophilic granulocyte percentage (NE%, 54.7%). The Bayes discriminant function demonstrated an initial validation accuracy of 74.9% and a cross-validation accuracy of 63.7%. The study underscores that hRSV, SARS-CoV-2, and HAdV are the primary pathogens in acute respiratory infections in the Shihezi region. Pathogen susceptibility exhibits variation across different age groups, with a higher pathogen detection rate in children compared to adults. The Bayes discriminant function shows significant promise in the classification and diagnosis of major pathogenic infections.