DEAD-box proteins are enzymes endowed with nucleic acid-dependent ATPase, RNA translocase and unwinding activities. The human DEAD-box protein DDX3 has been shown to play important roles in tumor proliferation and viral infections. In particular, DDX3 has been identified as an essential cofactor for HIV-1 replication. Here we characterized a set of DDX3 mutants biochemically with respect to nucleic acid binding, ATPase and helicase activity. In particular, we addressed the functional role of a unique insertion between motifs I and Ia of DDX3 and provide evidence for its implication in nucleic acid binding and HIV-1 replication. We show that human DDX3 lacking this domain binds HIV-1 RNA with lower affinity. Furthermore, a specific peptide ligand for this insertion selected by phage display interferes with HIV-1 replication after transduction into HelaP4 cells. Besides broadening our understanding of the structure-function relationships of this important protein, our results identify a specific domain of DDX3 which may be suited as target for antiviral drugs designed to inhibit cellular cofactors for HIV-1 replication.

Background: One of the five strategic directions in the World Health Organization global health sector strategy on viral hepatitis 2016-2021 is to generate strong strategic information for focused action to understand the viral hepatitis epidemic and focus the response. Knowledge of national prevalence is a cornerstone of strategic information. Germany is considered to be a low prevalence country for viral hepatitis B, C, and D, however the prevalence is likely to be higher among at-risk groups. Methods: The aim of this work was to give a detailed overview of the prevalence of viral hepatitis B (HBsAg, anti-HBc), C (anti-HCV, HCV RNA), and D (anti-HDV, HDV RNA) in different population groups in Germany. Therefore, we analyzed the results of a comprehensive literature search on various aspects of the epidemiological situation of hepatitis B, C, and D in Germany. Eligible publications including information on hepatitis B, C, and D prevalence were extracted from the overall spreadsheet table and summarized and analyzed based on virus and different population groups. A quality appraisal was performed using a checklist developed by Hoy et al. to assess risk of bias in prevalence studies. Results: Overall, 51 publications were identified through the literature search. The overall prevalence of HBsAg in the general (and proxy) population ranged from 0.3 to 1.6%. Among at-risk groups, including clinical populations and health care workers, the HBsAg prevalence ranged from 0.2% (among rheumatic patients) to 4.5% among HIV positive patients. The overall prevalence of anti-HCV in the general (and proxy) population ranged from 0.2 to 1.9%. Among at-risk groups, including clinical populations and health care workers, the anti-HCV prevalence ranged from 0.04% (among health care workers) to 68.0% among people who inject drugs. Conclusions: The hepatitis B and C prevalence in the general population in Germany is low. Prevalence is high to very high among at-risk populations, however for some Sperle et al. Hepatitis B, C, and D Prevalence groups evidence was incomplete or missing completely. To reach the elimination goals in Germany and implement a targeted response, more research among at-risk groups is needed.

Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high intrinsic mutation and replication rates of HIV-1 often lead to the emergence of drug resistant strains and consequent therapeutic failure. On this basis, cellular cofactors represent attractive new targets for HIV-1 chemotherapy, since targeting a cellular factor that is required for viral replication should help to overcome the problem of viral resistance. We and others have recently reported the identification of compounds suppressing HIV-1 replication by targeting the cellular DEAD-box helicase DDX3. These results provide a proof-of-principle for the feasibility of blocking HIV-1 infection by rendering the host cell environment less favorable for the virus. The rationale for such an approach and its implications in potentially overcoming the problem of drug resistance related to drugs targeting viral proteins will be discussed in the context of the known cellular functions of the DEAD-box helicase DDX3.

BackgroundGermany is considered to be a low prevalence country for viral Hepatitis B, C and D (HBV, HCV, HDV). However, the burden of disease can be high among subpopulations. To meet the world Health Organization (WHO) viral hepatitis (VH) elimination goals, a national strategy was developed by the German government in 2016. We performed a scoping review to understand the baseline epidemiological situation in Germany regarding burden of disease, sequelae and care of HBV, HCV and HDV as a reference to monitor the progress of the national VH elimination and to identify further knowledge gaps and research needs.

Background: Since the beginning of the Ebola outbreak in West Africa in 2014, more than 11,000 people died. For outbreaks of infectious diseases like this, the rapid implementation of control measures is a crucial factor for containment. In West African countries, outbreak surveillance is a paper-based process with significant delays in forwarding outbreak information, which affects the ability to react adequately to situational changes. Our objective therefore was to develop a tool that improves data collection, situation assessment, and coordination of response measures in outbreak surveillance processes for a better containment. Methods:We have developed the Surveillance and Outbreak Response Management System (SORMAS) based on findings from Nigeria's 2014 Ebola outbreak. We conducted a thorough requirements engineering and defined personas and processes. We also defined a data schema with specific variables to measure in outbreak situations. We designed our system to be a cloud application that consists of interfaces for both mobile devices and desktop computers to support all stakeholders in the process. In the field, health workers collect data on the outbreak situation via mobile applications and directly transmit it to control centers. At the control centers, health workers access SORMAS via desktop computers, receive instant updates on critical situations, react immediately on emergencies, and coordinate the implementation of control measures with SORMAS. Results:We have tested SORMAS in multiple workshops and a field study in July 2015.Results from workshops confirmed derived requirements and implemented features, but also led to further iterations on the systems regarding usability. Results from the field study are currently under assessment. General feedback showed high enthusiasm about the system and stressed its benefits for an effective outbreak containment of infectious diseases.Conclusions: SORMAS is a software tool to support health workers in efficiently handling outbreak situations of infectious diseases, such as Ebola. Our tool enables a bi-directional exchange of situational data between individual stakeholders in outbreak Perscheid et al. Ebola Outbreak Containment With SORMAS containment. This allows instant and seamless collection of data from the field and its instantaneous analysis in operational centers. By that, SORMAS accelerates the implementation of control measures, which is crucial for a successful outbreak containment.