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Zinc oxide (ZnO) tetrapods as microparticles with nanostructured surfaces show peculiar physical properties and anti-infective activities. The aim of this study was to investigate the antibacterial and bactericidal properties of ZnO tetrapods in comparison to spherical, unstructured ZnO particles. Additionally, killing rates of either methylene blue-treated or untreated tetrapods and spherical ZnO particles for Gram-negative and Gram-positive bacteria species were determined. ZnO tetrapods showed considerable bactericidal activity against Staphylococcus aureus, and Klebsiella pneumoniae isolates, including multi-resistant strains, while Pseudomonas aeruginosa and Enterococcus faecalis remained unaffected. Almost complete elimination was reached after 24 h for Staphylococcus aureus at 0.5 mg/mL and Klebsiella pneumoniae at 0.25 mg/mL. Surface modifications of spherical ZnO particles by treatment with methylene blue even improved the antibacterial activity against Staphylococcus aureus. Nanostructured surfaces of ZnO particles provide active and modifiable interfaces for the contact with and killing of bacteria. The application of solid state chemistry, i.e., the direct matter-to-matter interaction between active agent and bacterium, in the form of ZnO tetrapods and non-soluble ZnO particles, can add an additional principle to the spectrum of antibacterial mechanisms, which is, in contrast to soluble antibiotics, depending on the direct local contact with the microorganisms on tissue or material surfaces.

ZusammenfassungDie COVID-19-Pandemie stellt das deutsche Meldewesen im öffentlichen Infektionsschutz vor große Herausforderungen. Im Bundesland Schleswig-Holstein unterstützt die Landesmeldestelle die Gesundheitsämter durch tägliche und wöchentliche Auswertungen und hilft bei der Übermittlung der Meldedaten gemäß Infektionsschutzgesetz an das Robert Koch-Institut.In dem vorliegenden Bericht der Landesmeldestelle Schleswig-Holstein werden die SARS-CoV-2-Meldedaten aus dem Zeitraum März bis September 2020 ausgewertet. In Orientierung an der Entwicklung der Infektionszahlen wurde der Zeitraum in zwei Phasen ähnlichen Umfangs eingeteilt: März bis Mai und Juni bis September. Insgesamt wurden 4898 Infektionsfälle gemeldet. Bei dem Vergleich der Phasen zeigten sich besonders deutliche Unterschiede hinsichtlich der Hospitalisierung und Letalität, des Alters und der Staaten des Infektionsorts. In der ersten Phase waren besonders ältere Personen von einer hohen Hospitalisierungsrate und Sterblichkeit betroffen. In der zweiten Phase lagen das durchschnittliche Alter und die Hospitalisierungs- und Sterberaten deutlich niedriger und ein besonders großer Anteil war mit internationaler Reiseaktivität verbunden. Die Auswertung der Ausbruchsdokumentationen ergab den besonderen Schwerpunkt im Setting der privaten Haushalte. Dieser Artikel beschreibt die epidemische Situation in einem im Bundesvergleich Niedriginzidenzland.

The COVID-19 pandemic poses major challenges for the German notification system in public infection control. For the federal state of Schleswig-Holstein evaluations, the state reporting office supports the public health departments by providing daily and weekly evaluations and supports the transmission of notification data to the Robert Koch Institute according to the Infection Protection Act.In the present report of the state notification office of Schleswig-Holstein, the SARS-CoV‑2 reporting data for the period from March to September 2020 are evaluated. Based on the development of the infection numbers, this period was divided into two phases of similar size: March to May and June to September. A total of 4898 infection cases were reported. Upon comparison of the phases, there were particularly marked differences in hospitalization and mortality, age, and countries of infection site. In the first phase, elderly persons were particularly affected by high rates of hospitalization and mortality. In the second phase, the average age and hospitalization and mortality rates were significantly lower, and a particularly large proportion were associated with international travel activity. The evaluation of the outbreak documentation revealed a particular focus in private household settings. This article describes the epidemic situation in a low-incidence state within the Federal Republic of Germany.Die COVID-19-Pandemie stellt das deutsche Meldewesen im öffentlichen Infektionsschutz vor große Herausforderungen. Im Bundesland Schleswig-Holstein unterstützt die Landesmeldestelle die Gesundheitsämter durch tägliche und wöchentliche Auswertungen und hilft bei der Übermittlung der Meldedaten gemäß Infektionsschutzgesetz an das Robert Koch-Institut.In dem vorliegenden Bericht der Landesmeldestelle Schleswig-Holstein werden die SARS-CoV-2-Meldedaten aus dem Zeitraum März bis September 2020 ausgewertet. In Orientierung an der Entwicklung der Infektionszahlen wurde der Zeitraum in zwei Phasen ähnlichen Umfangs eingeteilt: März bis Mai und Juni bis September. Insgesamt wurden 4898 Infektionsfälle gemeldet. Bei dem Vergleich der Phasen zeigten sich besonders deutliche Unterschiede hinsichtlich der Hospitalisierung und Letalität, des Alters und der Staaten des Infektionsorts. In der ersten Phase waren besonders ältere Personen von einer hohen Hospitalisierungsrate und Sterblichkeit betroffen. In der zweiten Phase lagen das durchschnittliche Alter und die Hospitalisierungs- und Sterberaten deutlich niedriger und ein besonders großer Anteil war mit internationaler Reiseaktivität verbunden. Die Auswertung der Ausbruchsdokumentationen ergab den besonderen Schwerpunkt im Setting der privaten Haushalte. Dieser Artikel beschreibt die epidemische Situation in einem im Bundesvergleich Niedriginzidenzland.

Herpesvirus Macaca arctoides (HVMA) has the propensity to transform macaque lymphocytes to lymphoblastoid cells (MAL-1). Inoculation of rabbits with cell-free virus-containing supernatant resulted in the development of malignant lymphomas and allowed isolation of immortalised HVMA-transformed rabbit lymphocytes (HTRL). In this study, the HVMA genome sequence (approx. 167 kbp), its organisation, and novel aspects of virus latency are presented. Ninety-one open reading frames were identified, of which 86 were non-repetitive. HVMA was identified as a Lymphocryptovirus closely related to Epstein-Barr virus, suggesting the designation as 'Macaca arctoides gammaherpesvirus 1' (MarcGHV-1). In situ lysis gel and Southern blot hybridisation experiments revealed that the MAL-1 cell line contains episomal and linear DNA, whereas episomal DNA is predominantly present in HTRL. Integration of viral DNA into macaque and rabbit host cell genomes was demonstrated by fluorescence in situ hybridisation on chromosomal preparations. Analysis of next-generation sequencing data confirmed this finding. Approximately 400 read pairs represent the overlap between macaque and MarcGHV-1 DNA. Both, MAL-1 cells and HTRL show characteristics of a polyclonal tumour with B- and T-lymphocyte markers. Based on analysis of viral gene expression and immunohistochemistry, the persistence of MarcGHV-1 in MAL-1 cells resemble the latency type III, whereas the expression pattern observed in HTRL was more comparable with latency type II. There was no evidence of the presence of STLV-1 proviral DNA in MAL-1 and HTRL. Due to the similarity to EBV-mediated cell transformation, MarcGHV-1 expands the available in vitro models by simian and rabbit cell lines.

Advanced wound scaffolds that integrate active substances to treat chronic wounds have gained significant recent attention. While wound scaffolds and advanced functionalities have previously been incorporated into one medical device, the wirelessly triggered release of active substances has remained the focus of many research endeavors. To combine multiple functions including light-triggered activation, antiseptic, angiogenic, and moisturizing properties, a 3D printed hydrogel patch encapsulating vascular endothelial growth factor (VEGF) decorated with photoactive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles is developed. To achieve the smart release of VEGF, t-ZnO is modified by chemical treatment and activated through ultraviolet/visible light exposure. This process would also make the surface rough and improve protein adhesion. The elastic modulus and degradation behavior of the composite hydrogels, which must match the wound healing process, are adjusted by changing t-ZnO concentrations. The t-ZnO-laden composite hydrogels can be printed with any desired micropattern to potentially create a modular elution of various growth factors. The VEGF-decorated t-ZnO-laden hydrogel patches show low cytotoxicity and improved angiogenic properties while maintaining antibacterial functions in vitro. In vivo tests show promising results for the printed wound patches, with less immunogenicity and enhanced wound healing.

Human cytomegalovirus (HCMV) is a widespread human pathogen that causes asymptomatic infection in healthy individuals but poses a serious threat to immunocompromised patients. During the late phase of HCMV infection, the viral capsid is transported to the cytoplasmic viral assembly center (cVAC), where it is enclosed by the tegument protein layer and the viral envelope. The cVAC consists of circularly arranged vesicles from the trans -Golgi and endosomal networks. The HCMV gene UL35 encodes ppUL35 and its shorter form, ppUL35A. We have previously shown that the UL35 gene is involved in HCMV assembly, but it is unknown how UL35 proteins regulate viral assembly. Here we show that sorting nexin 5 (SNX5), a component of the retromer and part of the retrograde transport pathway, interacts with UL35 proteins. Expression of wild-type proteins but not mutants defective in SNX5 binding resulted in the cellular redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR), indicating that UL35 proteins bind and negatively regulate SNX5 to modulate cellular transport pathways. Furthermore, binding of UL35 proteins to SNX5 was required for efficient viral replication and for transport of the most abundant HCMV glycoprotein B (gB; gpUL55) to the cVAC. These results indicate that ppUL35 and ppUL35A control the localization of the essential gB through the regulation of a retrograde transport pathway. Thus, this work is the first to define a molecular interaction between a tegument protein and a vesicular transport factor to regulate glycoprotein localization. IMPORTANCE Human cytomegalovirus is ubiquitously present in the healthy population, but reactivation or reinfection can cause serious, life-threatening infections in immunocompromised patients. For completion of its lytic cycle, human cytomegalovirus induces formation of an assembly center where mature virus particles are formed from multiple viral proteins. Viral glycoproteins use separate vesicular pathways for transport to the assembly center, which are incompletely understood. Our research identified a viral structural protein which affects the localization of one of the major glycoproteins. We could link this change in glycoprotein localization to an interaction of the structural protein with a cellular protein involved in regulation of vesicle transport. This increases our understanding of how the virus intersects into cellular regulatory pathways to enhance its own replication.

In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of en passant mutagenesis was used. Targeted mutations within ORF36 and/or ORF28 and an autonomously expressed gene of the monomeric red fluorescent protein for plaque identification were introduced into the European wild-type VZV strain HJO. Plaque reduction assays revealed that the amino acid substitutions with unknown functions in TK, Q303stop, N334stop, A163stop, and the deletion of amino acids 7 to 74 aa (Δaa 7 to 74), were associated with resistance against acyclovir (ACV), penciclovir, or brivudine, whereas the L73I substitution and the Pol substitutions T237K and A955T revealed sensitive viral phenotypes. The results were confirmed by quantitative PCR by measuring the viral load under increasing ACV concentrations. In conclusion, analyzing the enzymatic activities of recombinant TK proteins represent a useful tool for evaluating the significance of amino acid substitutions in the antiviral resistance of clinical VZV strains. However, direct testing of replication-competent viruses by the introduction of nonsynonymous mutations in a VZV bacterial artificial chromosome using en passant mutagenesis led to reliable phenotypic characterization results.

Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17+ that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay. The strains were also tested for their aciclovir susceptibility by measuring the relative fluorescence intensity as an indicator for HSV-1 replication and by quantifying the virus yield. Our data indicate that the amino acid substitutions R41H, R106H, A118V, L139V, K219T, S276R, L298R, S345P, and V348I represent natural polymorphisms of the TK protein, whereas G61A and P84L mediate broad cross-resistance against aciclovir, penciclovir, brivudin, and susceptibility to foscarnet. This method allows the definition of the resistance genotype of otherwise unclear mutations in the TK gene of HSV-1. Thus, it provides a scientific basis for antiviral testing in clinical isolates of patients suffering from serious diseases and will facilitate testing of new antivirals against HSV-1.