Human Adenovirus Research Articles

Oral USC-093, a novel homoserinamide analogue of the tyrosinamide (S)-HPMPA prodrug USC-087 has decreased nephrotoxicity while maintaining antiviral efficacy against human adenovirus infection of Syrian hamsters

Adenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. Presently, there is no drug specifically approved for the treatment of adenovirus infections by the FDA. The state-of-the-art treatment of such infections is the off-label use of cidofovir, an acyclic nucleotide phosphonate. While cidofovir inhibits adenovirus replication, it has dose-limiting kidney toxicity. There is an apparent need for a better compound to treat adenovirus infections. To this end, we have been developing acyclic nucleotide phosphonate prodrugs that utilize an amino acid scaffold equipped with a lipophilic modifier. Here, we compare the antiviral potential of two prodrugs of HPMPA that differ only in the amino acid-based promoiety: USC-087, based on an N-hexadecyl tyrosinamide, and USC-093, based on an N-hexadecyl serinamide. Oral administration of both compounds was very efficacious against disseminated HAdV-C6 infection in immunosuppressed Syrian hamsters, suppressing virus replication and mitigating pathology even when treatment was withheld until 4 days after challenge. We saw only marginal efficacy after respiratory infection of hamsters, which may reflect suboptimal distribution to the lung. Importantly, neither compound induced intestinal toxicity, which was observed as the major adverse effect in clinical trials of brincidofovir, a prodrug of cidofovir which also contains a C-16 modifier. Notably, we found that there was a significant difference in the nephrotoxicity of the two compounds: USC-087 caused significant kidney toxicity while USC-093 did not, at effective doses. These findings will be valuable guidepoints in the future evolution of this new class of potential prodrugs to treat adenovirus infections.

Rapid detection of human adenovirus subgroup B using recombinase polymerase amplification assay.

Human adenovirus subgroup B (HAdV B) is one of the major pathogens of human respiratory virus infections, which has considerable transmission and morbidity in a variety of populations. Therefore, rapid and specific detection of HAdV B in clinical samples is essential for diagnosis. This study aimed to develop a product for rapid nucleic acid detection of HAdV B using recombinase polymerase amplification assay (RPA) and validate the performance of this method by using clinical samples. Results showed that this method achieved a lower limit of detection (LOD) of 10 copies/μL and had no cross-reactivity with other adenovirus subgroups or respiratory pathogens. In addition to high sensitivity, it can be completed within 30min at 40°C. There is no need to perform nucleic acid extraction on clinical samples. Taking qPCR as the gold standard, the RPA assay possessed a high concordance (Cohen's kappa, 0.896; 95% CI 0.808-0.984; P < 0.001), with a sensitivity of 87.80% and a specificity of 100.00%. The RPA assay developed in this study provided a simple and highly specific method, making it an important tool for rapid adenovirus nucleic acid detection and facilitating large-scale population screening in resource-limited settings.

NEAR INFRARED-RESPONSIVE HYDROGELS CONTAINING ADENOVIRAL VECTORS: APPLICATION IN BONE REGENERATION

We have developed plasmonic fibrin-based hydrogels that incorporate gold nanoparticles which transduce incident near-infrared (NIR) light into heat. Human adenovirus serotype type-5 vectors encoding a firefly luciferase (fLuc) coding sequence driven by a heat-inducible promoter were incorporated into the hydrogels. Transmission electronic microscopic analysis revealed that the adenoviral vectors were associated to the fibrin fibers. In vitro experiments in which human cells were cultured with plasmonic hydrogels showed that the adenoviral vectors can diffuse from the hydrogels, transduce the cells, and stimulate heat-induced transgene expression upon NIR irradiation. The hydrogels were implanted in 4.2 mm drill hole defects generated in the humerus of male rabbits. Three days after implantation, the defects were NIR-irradiated. Six h later, the animals were euthanized and samples from the bone defect zone were processed for immunohistochemical analyses using a specific fLuc antibody. The results showed strong expression of fLuc in tissues surrounding the implants of NIR-irradiated rabbits, while non- irradiated animals exhibited negligible expression. We next aimed to use the temperature increase to induce the production of transgenic bone morphogenetic protein 6 (BMP-6), using safe gene switches that can provide tighter control of in vivo transgene expression than heat-inducible promoters. These switches are only activated by heat in the presence of rapamycin and maintain a high level of targeted transgene expression for several days after heat activation. Adenoviral vectors encoding the safe switches that control the expression of BMP-6 were incorporated to the composites. The resulting NIR-responsive hydrogels were implanted in the bone defects generated in rabbits and used as a platform to transduce host cells, generate local hyperthermia and stimulate BMP-6 production.Acknowledgements: This research was supported by grants RTI2018-095159-B-I00 and PID2021-126325OB-I00 (MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”), by grant P2022/BMD- 7406 (Regional Government of Madrid). M.A.L-J. is the recipient of predoctoral fellowship PRE2019-090430 (MCIN/AEI/10.13039/501100011033).

Severe lower respiratory tract infections are associated with human adenovirus in hospitalised children in a high HIV prevalence area.

Viral causes of lower respiratory tract infections (LRTIs) are associated with increased mortality in children aged <5 years (U5). Human adenovirus (HAdV) has been associated with severe LRTI; however, its relationship with HIV and malnutrition in South Africa (SA) is not understood. To identify the prevalence of and factors associated with HAdV LRTIs in hospitalised U5 childen. Clinical and viral data on U5 children hospitalised with severe LRTI from January 2018 to June 2020 at King Edward VIII Hospital, Durban, SA, including results of a multiplex polymerase chain reaction (PCR) panel assay for respiratory viruses, were retrieved from inpatient files and laboratory databases and retrospectively analysed. Standard descriptive statistics and Pearson's χ², Fisher's exact and Mann-Whitney tests were used to determine significant associations with HAdV LRTI. Among the 206 viral assays analysed (15.6% of all LRTI admissions), HAdV was the most common virus identified. The cohort had a median (interquartile range) age of 5 (2 - 13) months, 47.3% had perinatal HIV exposure, and 34.5% had severe acute malnutrition (SAM). No seasonal pattern with HAdV could be demonstrated. SAM and prematurity were significant risk factors for readmission, and perinatal HIV exposure was a significant risk factor for presence of multiple viruses on analysis of a respiratory specimen. Detection of HAdV was not associated with an increased risk of requiring oxygen or ventilatory support. HAdV was the most common virus found on analysis of multiplex PCR panel results in children hospitalised with severe LRTI in SA, where high rates of HIV exposure may result in increased susceptibility to viral co-infections. The role of HAdV as a cause of severe LRTI in SA infants, who have high rates of HIV exposure, requires greater scrutiny. What the study adds. This study provides retrospective data identifying human adenovirus (HAdV) as the most common cause of severe lower respiratory tract infection (LRTI) in children aged <5 years (U5). The impact of respiratory syncytial virus as a common pathogen in children is well established. The study confirms anecdotal evidence that HAdV is an important disease-causing pathogen associated with LRTI. Children with perinatal HIV exposure and severe acute malnutrition (SAM) may be particularly susceptible.Implications of the findings. HAdV must be considered a major cause of severe LRTI in U5 children. Children with LRTI who had perinatal HIV exposure and those with SAM need to be tested for HAdV and to be monitored for severe disease.

Epidemiology and molecular detection of human adenovirus and non-polio enterovirus in fecal samples of children with acute gastroenteritis: A five-year surveillance in northern Brazil.

Acute gastroenteritis (AGE) is a common pediatric infection that remains a significant cause of childhood morbidity and mortality worldwide, especially in low-income regions. Thus, the objective of this study was to detect human adenovirus (HAdV) and non-polio enterovirus (NPEV) in fecal samples from the Gastroenteritis Surveillance Network, and to identify circulating strains by nucleotide sequencing. A total of 801 fecal samples were tested using qPCR/RT-qPCR, and 657 (82.0%) were inoculated into HEp-2C and RD cell lines. The HAdV and NPEV positivity rates obtained using qPCR/RT-qPCR were 31.7% (254/801) and 10.5% (84/801), respectively, with 5.4% (43/801) co-detection. Cytopathic effect was observed in 9.6% (63/657) of patients, 2.7% (18/657) associated with HAdV, and 6.2% (41/657) associated with NPEV after testing by ICC-PCR. A comparison of the two methodologies demonstrated an agreement of 93.5% for EVNP and 64.4% for HAdV. These two viruses were detected throughout the study period, with HAdV positivity rates ranging from 41% in Amapá to 18% in Pará. The NEPV varied from 18% in Pará/Rondônia to 3% in Acre. The most affected age group was over 60 months for both HAdV and NPEV. Samples previously positive for rotavirus and norovirus, which did not show a major difference in the presence or absence of diarrhea, fever, and vomiting, were excluded from the clinical analyses of these two viruses. These viruses circulated over five years, with a few months of absence, mainly during the months corresponding to the waves of SARS-CoV-2 infection in Brazil. Five HAdV species were identified (A, B, C, D, and F), with a greater predominance of HAdV-F41 (56.5%) followed by HAdV-C (15.2%). Three NPEV species (A, B, and C) were detected, with serotypes E14 (19.3%) and CVA-24 (16.1%) being the most prevalent. The present study revealed a high diversity of NPEV and HAdV types circulating in children with AGE symptoms in the northern region of Brazil.

Genotypes and Phylogenetic Analysis of Human Adenovirus in Hospitalized Pneumonia and Influenza-Like Illness Patients in Jiangsu Province, China (2013-2021).

Human adenovirus (HAdV) is common pathogens that cause various respiratory diseases. The genetic diversity of viruses caused by recombination is considered to be the main source of emerging outbreaks. The aim of this study is to explore the evolutionary relationship and recombination events of HAdV genome in respiratory tract infections in Jiangsu Province. Whole-genome sequencing (WGS) technology was used to sequence 66 patients with HAdV infection (37 patients with influenza-like illness (ILI) and 29 hospitalized patients with pneumonia) from Jiangsu Province. Epidemiological analysis was performed on hospitalized pneumonia and ILI patients infected with HAdV. Subsequently, phylogenetic, recombination, and nucleotide and amino acid identity analyses were performed. Epidemiological analysis of patients undergoing WGS showed that 75.7% of ILI patients were infected with the HAdVB strain and 69.0% of hospitalized pneumonia patients were infected with the HAdVC strain. Moreover, the hospitalized pneumonia and ILI patients infected with HAdV were different in region and time. The strains of HAdVB3 and HAdVB7 genotypes were mainly infected in 2015 and 2017, and the strains of HAdVC1 and HAdVC2 genotypes were mainly infected in 2020. The results of histogram analysis showed that the HAdV strain mainly infected children under 5 years old. In addition, 36 novel recombinant strains were identified. The discovery of these recombinant strains may contribute to understanding the epidemiology of HAdV and research on related vaccines. Furthermore, the percentage of nucleotide and amino acid identities revealed a high level of genetic conservation within isolates from HAdVB3, HAdVB7, HAdVC1, HAdVC2 and HAdVC5 genotypes. The WGS analysis reveals the evolutionary relationships and recombination events of HAdV strains in Jiangsu Province, which is helpful to deepen the understanding of HAdV epidemiology and evolution. In addition, it provides a basis for the formulation of public health strategies in Jiangsu Province.

Detection of Human Adenovirus from Clinical Samples of Conjunctivitis by Real-time PCR: A Cross-sectional Descriptive Study

Introduction: Human Adenoviruses (HAdV) have been implicated in a variety of infections, including conjunctivitis, respiratory tract infections, genitourinary infections and gastroenteritis. Epidemic Keratoconjunctivitis (EKC) is a severe ocular surface infection strongly associated with HAdV, known to occur in widespread outbreaks. HAdV species B, D and E are associated with ocular manifestations ranging from simple follicular conjunctivitis (types 3, 4, 7) and pharyngoconjunctival fever (types 3, 7, 14) to the more severe EKC (types 8, 19, 37, 53, 54, 56 and 64). Viral cell cultures of conjunctival specimens help confirm adenovirus infection through the characteristic Cytopathic Effect (CPE) and Polymerase Chain Reaction (PCR) is the best standard method to diagnose viral conjunctivitis due to its sensitivity, accuracy and rapidity. Aim: To diagnose HAdV in clinically suspected cases of viral conjunctivitis using real-time PCR. To isolate HAdV in viral cell culture and confirm it by observing its characteristic CPE and performing adenoviral real-time PCR. Materials and Methods: A cross-sectional descriptive study was conducted from July 2023 to September 2023 at the state-level Virus Research and Diagnostic Laboratory (VRDL) at Bangalore Medical College and Research Institute (BMCRI), Bengaluru, Karnataka, India. A total of 45 conjunctival swab samples from patients with suspected viral conjunctivitis, who attended the Ophthalmology Outpatient Department (OPD) or were admitted to the wards, were included in the study. Conjunctival swab samples collected in Viral Transport Medium (VTM) were centrifuged at 3000 rpm for five minutes at 4°C. Real-time PCR was performed and samples positive for HAdV by real-time PCR were taken up for viral cell culture. Confirmatory PCR was conducted for samples showing CPEs in the cell line. The data collected were analysed using descriptive statistics. Results: The majority of patients in the present study were in the age group of 18-45 years, comprising 25 (56%) of the total patients. Out of 45 conjunctival samples tested, 8 samples were positive in adenovirus real-time PCR. All eight PCR-positive samples showed a CPE in viral cell culture on the A549 cell line. The study found PCR positivity in 8 samples (17.7%), while adenoviral recovery from cell culture was observed in 6 samples (13.3%). Conclusion: Real-time PCR has become the standard diagnostic procedure for detecting adenovirus conjunctivitis. Rapid and accurate diagnosis is key to interrupting the contagious spread of adenoviral conjunctivitis, along with timely treatment.

Severe Adenovirus Infections in Young Adults

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Despite traditionally affecting individuals with compromised immune systems, severe human adenoviruses (HAdV) infections have been observed in young adults without immunodeficiency over recent decades.&lt;br /&gt;&lt;strong&gt;Case Presentation:&lt;/strong&gt; This case study documents two young patients infected with HAdV who experienced multi-organ failure,&lt;br /&gt;manifesting as respiratory distress, vasoplegia, myocardial injury, and kidney impairment. The resolution of organ failure&lt;br /&gt;correlated with the clearance of viral load, suggesting a potential prognostic indicator for infection outcomes. While the first&lt;br /&gt;case demonstrated a positive outcome with the resolution of viremia, regrettably, the second case succumbed to myocardial&lt;br /&gt;infarction followed by cardiac arrest. The use of cardiac monitoring may aid in the identification of significant myocardial&lt;br /&gt;complications associated with HAdV. Although various treatments, including the antiviral CIDOFOVIR, have been reported for&lt;br /&gt;immunocompromised individuals, it was not administered to our patients due to the favorable trajectory of the first case.&lt;br /&gt;Tragically, the second case passed away before any potential antiviral intervention could be initiated.&lt;br /&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;HAdV infections can cause severe acute respiratory distress syndrome with multi-organ failure including severe&lt;br /&gt;cardiac complications in young non-immunocompromised adults.&lt;/p&gt;

Genotypic diversity and long-term impact of human bocavirus on diarrheal disease: Insights from historical fecal samples in Brazil.

This study aimed to investigate the frequency and genotypic diversity of human bocavirus (HBoV) in historical fecal samples collected before 2005 in Brazil and understand its natural history in patients with diarrhea. Between 1998 and 2005, 3347 samples were tested for HBoV by RT-PCR, with a detection rate of 5.8% (195/3347). Coinfection with norovirus (NoV) and human adenovirus (HAdV) was found in 34.9% (68/195), indicating HBoV's potential role as a causative agent of diarrheal disease. The detection rate varied over the years (p < 0.05), suggesting natural oscillatory fluctuations. HBoV was more prevalent in fall and winter, with higher positivity in children ≤5 years (p < 0.05), reinforcing that HBoV is an important pathogen in childhood diarrhea. Genotyping (32.8%; 64/195) revealed the circulation of HBoV-1 (79.7%, 51/64), HBoV-3 (12.5%, 8/64), HBoV-2 (6.2%, 4/64), and the rare HBoV-4 (1.6%, 1/64). Difference in HBoV-1 and HBoV-2/-3 mono-infections prevalence (p < 0.05), suggests a potential role of HBoV-1 in the pathogenicity of diarrheal disease. The study highlights HBoV's lasting impact on viral gastroenteritis in Brazil and emphasizes its genotypic diversity. Recommending screening for HBoV in public health laboratories is crucial for understanding its role in gastrointestinal diseases. The data also contribute to understanding the molecular characterization of enteric viruses in historical fecal samples.

Prevalence of Parainfluenza Viruses in Seoul, 2021 - 2022.

Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.

Current antiviral agents against human adenoviruses associated with respiratory infections.

Human adenoviruses (HAdVs) are important pathogens responsible for respiratory infections. In children and immunocompromised patients, respiratory infections can cause considerable morbidity and mortality. Currently, there are no approved effective and safe antiviral therapeutics for the clinical treatment of HAdV infections, even those that have undergone preclinical/clinical trials. However, many compounds and molecules with anti-HAdV activity have been explored, and some candidates are undergoing clinical development. Here, we reviewed the reported in vitro and in vivo efficacies, as well as the therapeutic potential of these antiviral compounds, providing an overview and a summary of the current status of anti-HAdV drug development.

Respiratory syncytial virus among hospitalized patients of severe acute respiratory infection in Bhutan: Cross-sectional study.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, particularly in young children. In Bhutan, respiratory disease continues to be among the top 10 diseases of morbidity for several years. This study aimed to estimate the prevalence of RSV among hospitalized patients with severe acute respiratory infection (SARI) in Bhutan. Respiratory specimens were collected from SARI patients of all ages in 2016 and 2018 following influenza surveillance guidelines. Specimens were tested for influenza and RSV, human metapneumovirus, adenovirus, and human parainfluenza virus types 1, 2, and 3 using real-time reverse-transcription polymerase chain reaction assay. Descriptive statistics were used to analyze the result in STATA 16.1. Of the 1339 SARI specimens tested, 34.8% were positive for at least one viral pathogen. RSV was detected in 18.5% of SARI cases, followed by influenza in 13.4% and other respiratory viruses in 3%. The median age of SARI cases was 3 (IQR: 0.8-21 years)years. RSV detection was higher among children aged 0-6 (Adj OR: 3.03; 95% CI: 1.7-5.39) and 7-23 months (Adj OR: 3.01; 95% CI: 1.77-5.12) compared with the children aged 5-15 years. RSV was also associated with breathing difficulty (Adj OR: 1.73; 95% CI: 1.17-2.56) and pre-existing lung disease, including asthma (Adj OR: 2.78; 95% CI: 0.99-7.8). Respiratory viruses were detected in a substantial proportion of SARI hospitalizations in Bhutan.

Respiratory human adenovirus outbreak captured in wastewater surveillance

Respiratory adenovirus wastewater surveillance was compared to clinical data from a 2022 outbreak, showing a correlation with cases. Respiratory adenoviruses were less prevalent, with types 40/41 dominating. The schematic illustrates findings.

Faeco-prevalence of enteric viruses in children under five in Ogun State, Nigeria; a one-year study

Objective: Acute gastroenteritis has been reported as the second largest cause of preventable child mortality, accounting for an estimated annual 1.5 million deaths. In Nigeria, routine clinical diagnosis of infectious diarrhoea is bacterial-focused, leaving out the viral agents. Therefore, this study was designed to investigate the prevalence, seasonality, and risk factors of selected enteric viruses (EVs): human adenovirus (HAdV), norovirus (NoV), hepatitis A virus (HAV), and human astrovirus (HAstV) infection in children under 5 years old with acute gastroenteritis in Ogun State, Nigeria. Methods: One hundred faecal samples collected from out-patient diarrheal children under five years from six different hospitals between May 2021 and April 2022 were analysed using specific primers for four EVs by nested reverse transcription polymerase chain reaction. Result: Among the samples analysed, 44% were positive for at least one EV. The highest prevalence was recorded in HAdV (29%), followed by HAstV (9%), and NoV (6%). Mixed infections were only found in 3 cases. Additionally, the occurrence of EV infection was observed to be highest in children below 2 years (p = 0.002). A statistically significant (p = 0.03) association was observed between the EVs and the source of drinking water. The seasonal pattern of the EVs showed a marked increase in their incidence during the dry season. Conclusion: This study shows that EVs contribute to the burden of gastroenteritis in Ogun state, hence, continuous monitoring of these pathogens’ epidemiology remains fundamental to effective treatment and prevention of this disease.

Development of a Nanoplate-Based Digital PCR Test Method for Quantitative Detection of Human Adenovirus DNA.

Digital polymerase chain reaction (dPCR) assay is an advanced PCR technique that allows for the simultaneous detection and absolute quantification of diverse pathogens.Commercially validated kits available for detecting all subtypes of human adenovirus (HAdV) are limited. This study aimed to demonstrate the development of an in-house nanoplate-based dPCR assay with high sensitivity, even at low copy numbers. In this methodological study, the standardized HAdV DNA was prepared by amplifying the specific hexon gene region with real-time PCR and purifying the HAdV DNA using magnetic beads from HAdV-positive extractions. Dilutions were tested in triplicate during three independent runs to determine the dynamic range, the limit of detection (LoD), the limit of quantification (LoQ), precision, and reproducibility. The primer and probe sequences used in the study were selected based on a literature review to ensure the detection of all HAdV serotypes in a single run. The selected primers were verified using the US National Center for Biotechnology Information (NBCI) nBLAST tools, and the target sequence was determined using the BioEdit software. The DNA concentration of the stock solution was measured using a Qubit fluorometer. The estimated copy number of the stock solution per milliliter was calculated based on the length of the amplified base sequence and fluorometer measurement. The dynamic range of the test was determined to be from 770.4 to 0.9476 cp/μl, with the LoD and LoQ values both being 0.9476 cp/μl. The coefficient of determination (r 2) value of the test was 0.9986. The results demonstrated that the dPCR method could be an ideal tool for the diagnosis and absolute quantification of human adenoviruses, especially in low copy numbers. In order to determine the reproducibility of the test and validate the method for field use, it needs to be developed and adapted in various laboratories and supported by clinical studies.

A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within E1 or E3 genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both in vitro and in vivo and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs)- follicular helper T (Tfh) cells- germinal centre (GC) / memory B cells (MBCs)- long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the E1 and E3 genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.

Human adenovirus oncolytic properties and the inhibitory role of E4 orf4 and E4 orf6/7 on endogenously activated NF-κB

Human adenovirus is a promising tool for cancer therapy as an oncolytic virus. To predict which region of the oncolytic adenovirus E4 gene could be deleted, we investigated the relationship between the E4 proteins and NF-κB. Here, we report that TLR2-dependent NF-κB activation in Ad5-infected cells was significantly inhibited 24 h post-infection. Among the six E4 proteins, E4 orf4 and E4 orf6/7 exhibited notable suppressive effects on NF-κB activation. However, only E4 orf4 was co-immunoprecipitated with the RelA protein, also known as p65. It appears likely that E4 orf6/7 represses NF-κB activation via E2F-dependent pathways. Our results suggest that both E4 orf4 and E4 orf6/7 are novel inhibitors of NF-κB activation. The inhibition of endogenous NF-κB activation by E4 proteins during the late phase of infection also appears to elucidate the previously reported suppression of E1A expression in the late phase of infection. These redundant suppressive effects of E4 orf4 and E4 orf6/7 on NF-κB suggest that these proteins may play a major role in the anticancer properties of oncolytic adenovirus.

Recombinant human adenovirus p53 combined with transcatheter arterial chemoembolization for liver cancer: A meta-analysis.

To compare the clinical curative effects, survival and complications of recombinant human adenovirus-p53 (rAd-p53) combined with transcatheter arterial chemoembolization (TACE) versus TACE for the treatment of liver cancer. We searched all the eligible studies of rAd-p53 plus TACE versus control group had only TACE in the treatment of liver cancer, which were retrieved from CNKI, Wanfang database, CBM, VIP, PubMed, EMBase, The Chrance of Library, Web of Science from its inception to august 2022. A total of 17 studies were included, which involved 1045 patients. The results of the meta analysis indicated that the the rAd-p53combined with TACE markedly improved the patients' complete remission(OR = 2.19, 95% CI:1.13-4.22, P = 0.02), partial remission (OR = 2.22, 95% CI:1.67-2.94, P<0.00001), objective tumor response rate (OR = 2.58, 95% CI:1.95-3.41, P<0.00001) and disease control rate(OR = 2.39, 95% CI:1.65-3.47, P<0.00001) compared with TACE alone. And our results showed that rAd-p53combined with TACE had better survival benefit [6-month OS (OR = 3.41, 95% CI: 1.62-7.14, p = 0.001); 1-year OS (OR = 1.95, 95% CI: 1.28-2.96, p = 0.002)] and better quality of life(MD = 5.84, 95% CI:2.09-9.60, P = 0.002). In addition, the immunity of the patients was enhanced by the combination therapy, as demonstrated by the increase in the ratio of CD4+ to CD4+/CD8+. In adverse effects, except for fever in the TACE combined with rAd-p53 group, which was higher than that in the TACE group(OR = 2.62, 95% CI:2.02-3.49, P<0.00001), all other adverse effects were lower in the TACE combined with rAd-p53 group than in the TACE group. RAd-p53 combined with TACE for liver cancer showed significant advantages in terms of clinical efficacy, survival rate, and safety compared to the TACE alone, and effectively improved patient quality of life and immune function. https://inplasy.com/inplasy-2022-9-0127/.

Food and Environmental Virology: Use of Passive Sampling to Characterize the Presence of SARS-CoV-2 and Other Viruses in Wastewater.

Fecal shedding of SARS-CoV-2 leads to a renaissance of wastewater-based epidemiology (WBE) as additional tool to follow epidemiological trends in the catchment of treatment plants. As alternative to the most commonly used composite samples in surveillance programs, passive sampling is increasingly studied. However, the many sorbent materials in different reports hamper the comparison of results and a standardization of the approach is necessary. Here, we compared different cost-effective sorption materials (cheesecloths, gauze swabs, electronegative filters, glass wool, and tampons) in torpedo-style housings with composite samples. Despite a remarkable variability of the concentration of SARS-CoV-2-specific gene copies, analysis of parallel-deposited passive samplers in the sewer demonstrated highest rate of positive samples and highest number of copies by using cheesecloths. Using this sorption material, monitoring of wastewater of three small catchments in the City of Dresden resulted in a rate of positive samples of 50% in comparison with composite samples (98%). During the investigation period, incidence of reported cases of SARS-CoV-2 in the catchments ranged between 16 and 170 per 100,000 persons and showed no correlation with the measured concentrations of E gene in wastewater. In contrast, constantly higher numbers of gene copies in passive vs. composite samples were found for human adenovirus and crAssphage indicating strong differences of efficacy of methods concerning the species investigated. Influenza virus A and B were sporadically detected allowing no comparison of results. The study contributes to the further understanding of possibilities and limits of passive sampling approaches in WBE.

Increased circulation of human adenovirus in 2023: an investigation of the circulating genotypes, upper respiratory viral loads, and hospital admissions in a large academic medical center.

The circulation of human adenoviruses (HAdV) increased in 2023. In this manuscript, we show that HAdV-B3 was predominant in 2023 in a cohort characterized by the Johns Hopkins Hospital System. We also show that HAdV-B3 was associated with an increase in viral loads in respiratory samples and provide a correlation with the clinical presentations and outcomes.