Human Adenovirus Infection Research Articles

Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments.

A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions.

Human Adenovirus Type 7 Infections in Hubei, China During 2018-2019: Epidemic Features and Genetic Characterization of the Detected Viruses.

Human adenoviruses (HAdVs) type 7 can cause severe respiratory disease. During the period between December 2018 and August 2019, HAdV-7 infection was identified in 129 patients in Wuhan Children’s Hospital, Hubei Province, China. Samples were collected from hospitalized children and metagenomic sequencing was applied to detect the HAdV infections. Hemophagocytic lymphohistiocystosis (HLH) related to HAdV infections was observed in some patients clinically and patients were divided into two groups based on this to test the differences among clinical indicators. Genome variation, in silico restriction endonuclease analysis (REA), and phylogenetic analyses were carried out to show the genome characterization of HAdV-7 in this study. It was found that many indicators, such as all blood routine indicators, in patients of the HLH group showed significant levels. In this study, REA revealed that HAdV-7 might belong to genome 7d and genome variation analysis displayed the stable genome of HAdV. HAdV-7 is an ongoing threat to the public, and global surveillance should be established.

Adenovirus is prevalent in juvenile polyps and correlates with low vitamin D receptor expression.

BackgroundThe objective of this study was to assess human adenovirus (HAdV) infection in juvenile polyps (JPs) and to preliminarily establish a correlation to vitamin D receptor (VDR) expression.MethodsThe study includes 76 patients of 5.2 ± 2.8 years old. Seventy-eight JP specimens and 24 parapolyp tissues from polypectomy were used. PCR was used to detect HAdV DNA and quantitative reverse transcription-PCR for viral and host gene expression. The PCR products were sequenced for virus typing. The correlation between VDR expression and HAdV infection was established using nonparametric Spearman’s analysis.ResultsSeventy-four children (97.4%) had a single polyp and two had two polyps. The histopathological characteristics of the polyps were in line with JP. Thirty-three samples had HAdV DNA (43.4%), including 32 subgroup C and 1 subgroup B HAdV; no enteric HAdV was detected. HAdV messenger RNA was detected in 5 of the 33 samples (15.2%). The samples had increased interleukin-1β (IL-1β), IL-6, and calprotectin expression, and reduced E-cadherin and VDR expression. JP samples with low VDR expression were more prevalent of HAdV DNA (r = 1.261, 95% confidence interval, 1.017–1.563), while VDR expression positively correlated with E-cadherin and negatively with inflammation gene expression.ConclusionsHAdV latent infection was prevalent among JP tissues. The presence of HAdV correlated positively to low VDR expression.Impact The HAdVs infect the upper airways and gastrointestinal system and is found to persist in lymphoid tissues. The prevalence of HAdV and the status of the infection is unknown.The study investigated the prevalence of HAdV from polypectomy specimens of JP patients and found that HAdV was prevalent and was in a persistent state. HAdV infection was more prevalent in samples with low VDR expression.Whether HAdV infection and reactivation is a contributing factor to JPs is unknown. Factors such as proinflammation and bacterial metabolites that are known to promote HAdV reactivation warrant further investigation.

Molecular and epidemiological characterization of human adenovirus and classic human astrovirus in children with acute diarrhea in Shanghai, 2017\u20132018

BackgroundIn addition to rotavirus and norovirus, human adenovirus (HAdV) and classic human astrovirus (classic HAstV) are important pathogens of acute diarrhea in infants and young children. Here, we present the molecular epidemiology of HAdV and classic HAstV in children with acute diarrhea in Shanghai.MethodsFecal specimens were collected from 804 outpatient infants and young children diagnosed with acute diarrhea in Shanghai from January 2017 to December 2018. All of the samples were screened for the presence of HAdV and classic HAstV. HAdV and classic HAstV were detected using traditional PCR and reverse-transcription PCR, respectively. All of the HAdV and classic HAstV positive samples were genotyped by phylogenetic analysis.ResultsAmong the 804 fecal samples, 8.58% (69/804) of samples were infected with either HAdV or classic HAstV, and five were co-infected with two diarrhea viruses. The overall detection rates of HAdV and classic HAstV were 3.47% (28/804) and 5.22% (42/804), respectively. Four subgroups (A, B, C, and F) and seven genotypes (HAdV-C1, −C2, −B3, −C5, −A31, −F40, and -F41) of HAdV were detected. Subgroup F had the highest constituent ratio at 64.29% (18/28), followed by non-enteric HAdV of subgroup C (21.43%, 6/28) and subgroup B 10.71% (3/28). HAdV-F41 (60.71%, 17/28) was the dominant genotype, followed by HAdV-C2 (14.29%, 4/28) and HAdV-B3 (10.71%, 3/28). Two genotypes of classic HAstV (HAstV-1 and HAstV-5) were identified in 42 samples during the study period; HAstV-1 (95.24%, 40/42) was the predominant genotype, and the other two strains were genotyped as HAstV-5. No significant differences were found between boys and girls in the detection rates of HAdV (P = 0.604) and classic HAstV (P = 0.275). Over half of the HAdV infections (82.14%, 23/28) and classic HAstV infections (66.67%, 28/42) occurred in children less than 36 months. Seasonal preferences of HAdV and classic HAstV infections were summer and winter, respectively. In this study, the common clinical symptoms of children with acute diarrhea were diarrhea, vomiting, fever and abdominal pain.ConclusionsOur findings indicate that HAdV and classic HAstV play important roles in the pathogenesis of acute diarrhea in children in Shanghai. Systematic and long-term surveillance of HAdV and classic HAstV are needed to monitor their prevalence in children and prevent major outbreak.

Nonenteric Adenoviruses Associated with Gastroenteritis in Hospitalized Children.

ABSTRACTThe object of this study was to investigate the frequency of human adenovirus (HAdV) infections in hospitalized pediatric patients. Stool samples were collected during a 1-year period (February 2018 to January 2019). HAdV was detected by a broad-range PCR and genotyped by sequencing and phylogenetic analysis. Demographic characteristics and detailed clinical information were analyzed for each patient. HAdV was detected in 7.1% of stool samples (34/476). Among these patients, 23.5% were coinfected with other enteric viral or bacterial pathogens. The majority (85.2%) of HAdV positives were detected in children of <5 years of age. Two HAdV species (B and C) with three types were identified in this study population. HAdV species F was not detected. Genetic analysis shows that the isolates circulating in our region present high diversity and do not exhibit clonal expansion. The presence of nonenteric HAdV in subjects with gastrointestinal symptoms and in immunocompromised patients has already been reported by different studies and underlines the need to develop routine molecular assays that have wide reactivity for most types of adenovirus in order to obtain an optimal tool for their rapid and accurate diagnosis.IMPORTANCE Gastroenteritis is the second leading cause of death among infants and children worldwide. Our study shows that adenovirus types other than 40 and 41 might be related to acute gastroenteritis. Therefore, a novel approach using diagnostic methods able to detect all adenovirus types is desirable in order to overcome the limitations of the current techniques.

Molecular Characteristics of Human Adenovirus Type 3 Circulating in Parts of China During 2014–2018

Human adenoviruses (HAdVs) are important pathogens causing respiratory infections; 3.5–11% of childhood community-acquired pneumonia is associated with HAdV infection. Human adenovirus type 3 (HAdV-3), leading to severe morbidity and mortality, is one of the most prevalent genotype among adenoviruses responsible for acute respiratory infections (ARIs) in children in China. To identify the genetic variation of HAdV-3 in children with ARIs in China, a molecular epidemiological study was conducted. A total of 54 HAdV-3 isolated strains were obtained from children with ARIs in Beijing, Wenzhou, Shanghai, Shijiazhuang, Hangzhou, Guangzhou, and Changchun from 2014 to 2018. Thirty-two strains of which were selected for whole-genome sequencing, while the hexon, penton base, and fiber genes were sequenced for remaining strains. Bioinformatics analysis was performed on the obtained sequences. The phylogenetic analyses based on whole-genome sequences, major capsid protein genes (hexon, penton base, and fiber), and early genes (E1, E2, E3, and E4) showed that the HAdV-3 strains obtained in this study always clustered together with the reference strains from Chinese mainland, while the HAdV-3 prototype strain formed a cluster independently. Compared with the prototype strain, all strains possessed nine amino acid (AA) substitutions at neutralization antigenic epitopes of hexon. The homology models of the hexon protein of the HAdV-3 prototype and strain BJ20160214 showed that there was no evident structural change at the AA mutation sites. Two AA substitutions were found at the Arg-Gly-Asp (RGD) loop and hypervariable region 1 (HVR1) region of the penton base. A distinct AA insertion (20P) in the highly conserved PPPSY motif of the penton base that had never been reported before was observed. Recombination analysis indicated that partial regions of protein IIIa precursor, penton base, and protein VII precursor genes among all HAdV-3 strains in this study were from HAdV-7. This study showed that the genomes of the HAdV-3 strains in China were highly homologous. Some AA mutations were found at antigenic sites; however, the significance needs further study. Our data demonstrated the molecular characteristics of HAdV-3 circulating in China and was highly beneficial for further epidemiological exploration and the development of vaccines and drugs against HAdV-3.

Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC—EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.

Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression.

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1β, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the “cytokine storm” occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.

Molecular Investigation of the Human Adenovirus in Retinoblastoma Patients

Background and Aims: Retinoblastoma tumors are the most common intraocular malignancy in childhood, leading to death after two years. The Human Adenovirus (HAdV) infection could be critical in the retinoblastoma pathogenesis due to the virus and retinoblastoma 1 interactions. The objective of the current study was to investigate the possible presence of the HAdV genome in the retinoblastoma patient's tumors. Materials and Methods: In this study, we evaluated the HAdV infection in 96 pathological confirmed retinoblastoma samples. The DNA was extracted from formalin-fixed paraffin-embedded blocks, and the virus infection was assessed using polymerase chain reaction. SPSS version 22 was used for statistical analysis. Results: The mean age ± SD of the retinoblastoma patients was 28.89 ± 17 months. In addition, the demographic evaluation indicated that 43 (46.7%) of patients were female. The retinoblastoma laterality assessment indicates 87 (90.4%) unilateral and 9 (9.4%) bilateral tumors. Growth pattern analysis indicates endophytic 58 (77.3%), exophytic 8 (10.7%), and 9 (12%) of tumors with mix endophytic and exophytic patterns. The polymerase chain reaction results could not found any evidence of HAdV infection in all 96 formalin-fixed paraffin-embedded samples. Conclusions: The study results suggest that there is not any association between HAdV infection and retinoblastoma tumors in studied samples. The HAdV infection may not a concern in retinoblastoma pathogenesis. Further investigations are recommended in this field of study.

Epidemiology of enteric virus infections in children living in the Amazon region

ObjectivesTo verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix™ vaccination coverage in children from the Amazon region. DesignFecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix™ RVA vaccination data were recorded. ResultsNorovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0–2.3; P = 0.04) but not to RVA, norovirus or SaV infection. ConclusionsNorovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene.

Rapid identification and metagenomics analysis of the adenovirus type 55 outbreak in Hubei using real-time and high-throughput sequencing platforms

The rise in human adenovirus (HAdV) infections poses a serious challenge to public health in China. Real-time (RT) sequencing provides solutions for achieving rapid pathogen identification during outbreaks, whereas high-throughput sequencing yields higher sequence accuracy. In the present study, we report the outcomes of applying nanopore and BGI platforms in the identification and genomic analysis of an HAdV outbreak in Hubei province, China in May of 2019. A mixed sample of nine nasopharyngeal swabs and one single sample were submitted to direct nanopore sequencing (MinION device), generating their first HAdV-55 reads within 13 and 20min, respectively. The sequences were confirmed by RT-polymerase chain reaction (PCR). Ten HAdV-positive samples were further sequenced using next-generation high-throughput sequencing (BGISEQ-500 device). Phylogenetic analysis revealed that the outbreak strain had a close genetic relation to strains isolated in Sichuan province. Metagenomic analysis showed that HAdV-55 was not a dominant species in samples from which the whole HAdV-55 genome could not be assembled. The present results highlight the value of combining sequencing platforms and using mixed samples for nucleic acid enrichment in pathogen detection of infectious disease outbreaks.

RETRACTED ARTICLE: Immunoinformatic mapping of conserved regions of the human adenovirus hexon protein

Human Adenoviruses (HAdVs) are important infectious agents associated with high incidence and morbidity and mortality in immunocompromised patients, such as those undergoing allogeneic hematopoietic progenitor cell transplantation (allo-TCPH). HAdVs belong to the family Adenoviridae, genus Mastadenovirus, and are further classified into seven species (A–G) and 103 genotypes, characterized so far. The HAdV capsid consists mainly of the hexon protein, which has four highly conserved regions (CR1—4) and known for their immunogenic potential, being one of the main targets of the T and B cell-mediated anti-HAdV immune response of the present study was to perform the mapping of potentially immunogenic epitopes, located in the HAdV hexon CRs and to evaluate the HAdV infection in patients undergoing allo-TCPH. To this end, predictions of T and B cell epitopes and IFN-γ induction were performed, considering 101 HAdV genotypes with sequences available in databases. The most conserved and best-classified epitopes were then selected by the prediction programs to perform the molecular docking analysis with HLA alleles of the study population, consisting of nine adult patients undergoing allo-TCPH. It was also carried out the HAdV research by TaqMan real-time polymerase chain reaction (qPCR) in the patient's serum samples. As a result, regions containing overlapping T and B cell epitopes were obtained and, based on immunoinformatics analysis (prediction and molecular docking), two peptides with high conservation and immunogenic potential were designed. Nine patients were positive for HAdV by qPCR TaqMan, with the average viral load found in the serum samples of the study population being 6.71 × 1011 CG / mL. The genomic sequencing of the positive samples returned sequences that showed 100% similarity with sequences of the hexad protein of HAdV C, deposited in a database. The present study allowed the mapping of the main immunogenic regions located in the HAdV hexon CRs, as well as the construction of two peptides that will be used in future studies to assess the immune response of patients undergoing allo-TCPH, participants in the present study.

#18: Brincidofovir for the Treatment of Disseminated Human Adenovirus Infection in Pediatric Solid-organ Transplant Recipients

Abstract Background Human adenovirus (HAdV) viremia can cause significant morbidity among pediatric patients undergoing solid-organ transplantation (SOT). Currently, there are no US Food and Drug Administration (FDA)-approved treatments for HAdV infections, and historically the mainstay of treatment has been decreasing immunosuppression with antiviral therapies reserved for those with severe disease. Brincidofovir (BCV) is an investigational antiviral drug with potency against HAdV. We describe four cases of disseminated HAdV infection treated with (BCV) among pediatric SOT patients. Methods We retrospectively reviewed 4 cases of severe disseminated HAdV infection, which occurred between 2018 and 2019, in a tertiary pediatric transplant center. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. Baseline clinical characteristics, disease course, treatment, and outcomes were reviewed. Results Four pediatric SOT patients (2 kidneys, 1 dual kidney/liver, and 1 liver) ranging in age from 9 months to 19 years were diagnosed with HAdV infection (Table 1). Patients presented with varied symptoms from 12 to 912 days post-transplant. Peak HAdV viral load ranged from 37,000 to &amp;gt;1,000,000 copies/mL. All patients had disseminated disease with evidence of graft involvement and varying degrees of acute kidney injury (AKI) making them candidates for BCV therapy over cidofovir to avoid nephrotoxicity. Three out of four patients received cidofovir prior to conversion to BCV. IRB-approved compassionate use of BCV was dosed at 2 mg/kg (max 100 mg) twice weekly PO along with reduced immunosuppression. Resolution of symptoms and HAdV viremia was seen at a mean of 21.5 days (range 15–32) of therapy. All patients had resolution of AKI with a return to baseline creatinine after therapy. Conclusions Though HAdV infection in pediatric SOT patients is uncommon, a subset of patients experience severe disease, morbidity, and graft loss. Currently, HAdV is not routinely monitored in pediatric SOT transplant patients. Although supportive care and decreased immunosuppression remain as the most important component of therapy, BCV was well tolerated and efficacious in our series. Further research is needed to better understand risk factors for HAdV infection and potential antiviral treatment options to improve patient outcomes.

From Upper Respiratory Symptoms to Hemophagocytic Lymphohistiocytosis: Case Report of a Human Adenovirus Infection in Haploidentical Hematopoietic Stem Cell Transplant Recipient

Human adenovirus infection is rare in adult population, except for in immunocompromised individuals. Recipients of allogenic haploidentical hematopoietic stem cell transplantation are reported at high risk for human adenovirus, which is often lethal when it evolves into the disseminated form. Despite existent guidelines, prevention, early diagnosis, and therapeutics remain challenging. Here, we report the case of a fatal evolution of human adenovirus respiratory infection and discuss the actual recommendations to prevent recurrence of this major issue.

Repurposing antiviral drugs on recently emerged viral infections: A review article

Finer understandings of drugs, for newly emerged diseases are becoming difficult nowadays. The contemporary approach is Drug Repurposing. Drug repurposing implies the exploration of surviving drugs for new restorative motive. Apart from conventional drug approaches, it is a profitable, brisk and reliable approach. The equivalent therapies for newly emerging and remerging viral infections are strenuous spot these days. The drug repurposing has helped in treating many viral reprofiling infectious diseases like CoVID-19, MERS, SARS, Influenza, Swine flu, Hanta, Zika, Ebola, Marburg, Human Adeno virus infection etc. The present review looks at describing the drug repurposing approach in various viral infections.

Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome.

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

Which drugs to treat Adenovirus infections?

Human adenoviruses (HAdV) infections are generally mild and resolve spontaneously in immunocompetent individuals. However, HAdV infections can have a major clinical impact in immunocompromised patients. HAdV infections are associated with high morbidity and mortality in recipients of allogeneic stem cell transplants, particularly children. There are currently no drug approved for the treatment of HAdV infections. Nevertheless, some nucleotide analogues are used under temporary authorization for use, such as cidofovir or brincidofovir. Cidofovir inhibits the replication of HAdV but its nephrotoxicity and its low tissue concentrations severely limit its use. Brincidofovir, a cidofovir prodrug, with a better bioavailability and no nephrotoxicity was evaluated in the treatment of HAdV infections, but its development was recently stopped and it is currently no longer available in ATU. Other molecules with anti-HAdV activity are still in early stages of development. Adoptive immunotherapy by adenovirus-specific T-cell transfer is an interesting option but should be anticipated in patients with high risks of disseminated infections. Given the small therapeutic panel available, it is critical to continue the search for new anti-HAdV molecules, which remains mainly conducted by academic laboratories.

Emergence and characterization of a putative novel human adenovirus recombinant HAdV-C104 causing pneumonia in Southern China.

In 2017, a survey of the molecular epidemiology of human adenovirus (HAdV) infections in Southern China based on hexon and fiber genotype demonstrated that the most prevalent genotypes of HAdV were HAdV-3 (n = 62), HAdV-2 (n = 21), and HAdV-7 (n = 16). In addition, two patients were co-infected with two genotypes of HAdV. Interestingly, a novel human adenovirus C recombinant genotype strain was isolated from one of the pneumonia patients in this survey. Phylogenetic, recombination, and proteotyping analysis showed that this novel pathogen originated from the recombination of parental viruses harboring the HAdV-1 penton and hexon gene, and the HAdV-2 fiber gene. It was named ‘P1H1F2’ and was assigned as HAdV-C104 based on the nomenclature protocol of using three major capsid proteins for characterization. Subsequent in vitro experiments demonstrated that HAdV-C104 had comparable proliferation capacity to HAdV-1, HAdV-2, and another recombination genotype P1H2F2. In addition, the HAdV-C104 infected patient was diagnosed with pneumonia and recovered after antiviral therapy. This report strengthens the hypothesis of recombination as a major pathway for the molecular evolution of HAdV-C species.

Follow-up of human adenovirus viral load in pediatric hematopoietic stem cell transplant recipients.

The spectrum of human adenovirus (HAdV)-related disease is broad, and the virus acts on many organs and systems in hematopoietic stem cell transplantation (HSCT) recipients. We aimed to evaluate the effect of HAdV-DNA positivity with clinical and laboratory findings 4months after HSCT. We retrospectively investigated HAdV-DNA in 153 HSCT recipients (≤18years) by quantitative real-time polymerase chain reaction (RealStar; Altona Diagnostics). The results of samples from January 2014 to December 2017 are included. HAdV-DNA was positive for at least one sample type in 50 (32.67%) patients. HAdV-DNA positivity rate was 8.92% (N: 145/1625), 40.25% (N: 64/159), and 25% (N: 2/8) for plasma, stool, and urine samples, respectively. HAdV-DNA was positive in the plasma of 38 (24.83%) patients at a median 16 (range: 1-58days) days after HSCT. The mortality rate was 23.68% and 6.95% in plasma HAdV-positive and HAdV-negative patients (p=.014). Moreover, HAdV-DNA positivity had an impact on overall survival for allogeneic-HSCT (p=.013), with the cumulative effect including graft-versus-host disease state in multivariate analysis (p=.014). Plasma HAdV-DNA positivity is a potential influencer that decreases survival in the early post-transplant period. Due to the high mortality rates, close monitoring is required of HAdV infections after HSCT with sensitive methods, especially at the early stage.

Outbreaks of Acute Respiratory Disease Associated with Human Adenovirus Infection in Closed Camps, China, December 2011-March 2014.

What is already known on this topic?Human adenovirus (HAdV) was frequently associated with acute respiratory disease (ARD) outbreaks in military camps.What is added by this report?HAdV-B7, HAdV-B14, and HAdV-B55 were determined to be responsible for 3, 2, and 4 ARD outbreaks in military camps, China, respectively, with a total attack rate of 28.0% during 2011 to 2014.What are the implications for public health practice?The findings suggest that vaccine development and administration in military camps must be prioritized. Quarantining among new recruits before entering into the military and the identification of the major responsible genotypes at the current stage is warranted.