IV.—On the District of the Ancient Glaciers of the Isar and of the Linth

In order to interchange our views, and arrive at a common understanding on the question of the connection of glaciers with the formation of lakes, we undertook a joint excursion in Upper Bavaria, in the district of the Ammer Lake, Wuerm Lake, Staffel Lake, and Eieg Lake, and later, in the month of September, we visited together the shores of the Lake of Zurich, partly accompanied by Dr. K. I. V. Steenstrup, of Copenhagen, Dr. A. Wettstein and Dr. E. Brueckner, of Hamburg. We have drawn up a short protocol, both on the facts observed and of our views respecting them, which we here propose to communicat

Unique sequence features of the Human Adenovirus 31 complete genomic sequence are conserved in clinical isolates

<p>Abstract</p> <p>Background</p> <p>Human adenoviruses (HAdV) are causing a broad spectrum of diseases. One of the most severe forms of adenovirus infection is a disseminated disease resulting in significant morbidity and mortality. Several reports in recent years have identified HAdV-31 from species A (HAdV-A31) as a cause of disseminated disease in children following haematopoetic stem cell transplantation (hSCT) and liver transplantation. We sequenced and analyzed the complete genome of the HAdV-A31 prototype strain to uncover unique sequence motifs associated with its high virulence. Moreover, we sequenced coding regions known to be essential for tropism and virulence (early transcription units E1A, E3, E4, the fiber knob and the penton base) of HAdV-A31 clinical isolates from patients with disseminated disease.</p> <p>Results</p> <p>The genome size of HAdV-A31 is 33763 base pairs (bp) in length with a GC content of 46.36%. Nucleotide alignment to the closely related HAdV-A12 revealed an overall homology of 84.2%. The genome organization into early, intermediate and late regions is similar to HAdV-A12. Sequence analysis of the prototype strain showed unique sequence features such as an immunoglobulin-like domain in the species A specific gene product E3 CR1 beta and a potentially integrin binding RGD motif in the C-terminal region of the protein IX. These features were conserved in all analyzed clinical isolates. Overall, amino acid sequences of clinical isolates were highly conserved compared to the prototype (99.2 to 100%), but a synonymous/non synonymous ratio (S/N) of 2.36 in E3 CR1 beta suggested positive selection.</p> <p>Conclusion</p> <p>Unique sequence features of HAdV-A31 may enhance its ability to escape the host's immune surveillance and may facilitate a promiscuous tropism for various tissues. Moderate evolution of clinical isolates did not indicate the emergence of new HAdV-A31 subtypes in the recent years.</p

Evolution of Poliovirus Type I during 5.5 Years of Prolonged Enteral Replication in an Immunodeficient Patient

AbstractPoliovirus type 1 was isolated from an immunodeficient patient 4 days after onset of paresis (IS1) and after 5.5 years of prolonged enteral virus replication (IS2). Antigenic characterization revealed that IS1 was Sabin 1-like, whereas IS2 reacted like poliovirus 1 Mahoney. Complete genomic sequencing demonstrated the phylogenetic relationship (94.9% identity) of IS1 and IS2, which differed from the most closely related Sabin 1 by 5.4 and 8.3%, respectively. Both isolates had revertant-like mutations at nucleotides 480 and 6203. Deduced amino acid sequences indicated significant changes between IS1 and IS2 at the neutralizing antigenic site 1. Prolonged enteral replication, evolution, and shedding of poliovirus by immunodeficient patients should be considered in the poliovirus eradication strategy

Epidemic keratoconjunctivitis: efficacy of outbreak management

Purpose Epidemic keratoconjunctivitis (EKC) is one of the most severe ocular viral infections. The aim of this interruptive time series study was to quantitatively evaluate the effectiveness of a hygienic EKC outbreak management concept developed in our ophthalmological department. Methods All patients with suspected EKC in the period from August to November 2018 were included in the study. Data were retrospectively collected from the patient’s medical documents and records. The disease was diagnosed clinically and confirmed by virus detection through polymerase chain reaction (PCR) from conjunctival swabs. With the beginning of the epidemic, an outbreak management plan was implemented to reduce the nosocomial spread. Results The outbreak lasted 77 days (20th August 2018 to 4th November 2018) and affected a total of 120 patients. This corresponds to a mean of 1.5 patients per outbreak day. The median age was 58 [1–92] years. Of all patients, 61 (50.8%) were female. Conjunctival swabs were collected in 100/120 (83.3%) cases, the adenovirus being detected in all positive smears (63/63, 100%). The implementation of our outbreak management plan reduced significantly the number of EKC cases per outbreak day and resulted in a reduction of the basic reproduction number by a factor of 2.2. Conclusion The detection of EKC together with the immediate implementation of hygienic outbreak measures can significantly reduce the spread of infection. The implementation of a strict outbreak management concept can significantly reduce the number of EKC cases, thus avoiding possible complications and therefore unnecessary health-related costs

Discovery of immunodominant T-cell epitopes reveals penton protein as a second immunodominant target in human adenovirus infection

Additional file 2: Figure S2. Analysis of HAdV-specific T-cell responses against the novel immunodominant T-cell epitope in healthy donors

Linking digital surveillance and in-depth virology to study clinical patterns of viral respiratory infections in vulnerable patient populations

To improve the identification and management of viral respiratory infections, we established a clinical and virologic surveillance program for pediatric patients fulfilling pre-defined case criteria of influenza-like illness and viral respiratory infections. The program resulted in a cohort comprising 6,073 patients (56% male, median age 1.6 years, range 0–18.8 years), where every patient was assessed with a validated disease severity score at the point-of-care using the ViVI ScoreApp. We used machine learning and agnostic feature selection to identify characteristic clinical patterns. We tested all patients for human adenoviruses, 571 (9%) were positive. Adenovirus infections were particularly common and mild in children ≥1 month of age but rare and potentially severe in neonates: with lower airway involvement, disseminated disease, and a 50% mortality rate (n = 2/4). In one fatal case, we discovered a novel virus: HAdV-80. Standardized surveillance leveraging digital technology helps to identify characteristic clinical patterns, risk factors, and emerging pathogens.Peer Reviewe

Evidence of Molecular Evolution Driven by Recombination Events Influencing Tropism in a Novel Human Adenovirus that Causes Epidemic Keratoconjunctivitis

In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the ε determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the ε neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the ε determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus