VExD: A curated resource for human gene expression following viral infection

MotivationHuman viruses cause significant mortality, morbidity, and economic disruption worldwide. The human gene expression response to viral infection can yield important insights into the detrimental effects to the host. To date, hundreds of studies have performed genome-scale profiling of the effect of viral infection on human gene expression. However, no resource exists that aggregates human expression results across multiple studies, viruses, and tissue types.ResultsWe developed the Virus Expression Database (VExD), a comprehensive curated resource of transcriptomic studies of viral infection in human cells. We have processed all studies within VExD in a uniform manner, allowing users to easily compare human gene expression changes across conditions.Availability and ImplementationVExD is freely accessible at https://vexd.cchmc.org for all modern web browsers. An Application Programming Interface (API) for VExD is also available. The source code is available at https://github.com/pdexheimer/[email protected], [email protected]

TRACER: A toolkit to register and visualize anatomical coordinates in the rat brain

The need for anatomical registration and visualization tools is greater than ever thanks to novel technologies that allow users to record from thousands of neurons across multiple brain regions simultaneously. The vast majority of digital reconstruction toolkits for rodent models were developed using mouse brain atlases, leaving few options for those using rats. Retrofitting rat atlases into extant software is possible, but this demands effort and programming skills which most end-users lack. We therefore developed an open-source, python-based Toolkit for Reconstructing Anatomical CoordinatEs in Rats, TRACER, which allows users to reconstruct the trajectories of recording electrodes (e.g Neuropixels) or to visualize virus expression or other features in a comprehensively annotated 3D volume, the Waxholm Space (WHS) rat brain atlas. The WHS atlas is made from high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans, and contains >200 regional delineations. Beyond post-hoc reconstructions of electrodes or virus expression, TRACER can be used to generate coordinates for targeting brain regions prior to surgery. TRACER is available openly on GitHub and is compatible with Windows, macOS and Linux operating systems.

Exosome-mediated stable epigenetic repression of HIV-1

Human Immunodeficiency Virus (HIV-1) produces a persistent latent infection. Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost of life-shortening side effects and development of drug-resistant HIV-1. An ideal and safer therapy should be deliverable in vivo and target the stable epigenetic repression of the virus, inducing a stable “block and lock” of virus expression. Towards this goal, we developed an HIV-1 promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains of DNA methyltransferase 3 A to induce long-term stable epigenetic repression of HIV-1. Cells were engineered to produce exosomes packaged with RNAs encoding this HIV-1 repressor protein. We find here that the repressor loaded anti-HIV-1 exosomes suppress virus expression and that this suppression is mechanistically driven by DNA methylation of HIV-1 in humanized NSG mouse models. The observations presented here pave the way for an exosome-mediated systemic delivery platform of therapeutic cargo to epigenetically repress HIV-1 infection.

A Study On The Construction Of Virus Infection Area Information System Using Iomt Environment

With the recent emergence of novel virus, the importance has been empathized on the epidemiologic investigation of the infection route and control of infected patients. Control system on the viral infections is required since the new virus expression cycle becomes faster which was not previously identified with the spread to other regions and countries. Viral infections cause multiple types of problems such as public health, economic and social ones. In addition, viruses can be spread fast beyond the regions and countries all over the world according to the movements of population. Although national quarantine systems have been established to solve these problems by countries, earlier actions on the novel virus were not satisfactory. IoT environment-based healthcare industry and IT convergence medical service industry have been continuously growing. Healthcare IT, which is the area to deal with information on the personal health and medical cares, devices, systems, and platforms, provides with personal healthcare services. In this article, information system on the virus infected territories is proposed using Internet of Medical Things (IoMT) environment. The proposed study is to establish the information system on the virus infected territories by IoMT-based monitoring of infection symptoms for early reactions against the viral infections. The system can be reacted proactively by detecting the risk factors of community spread from early detections of infected patients under the fast spread situation of viral diseases. The information system on the virus infected territories using IoMT environment can react to the spread of infectious diseases actively upon providing the information of infectious disease symptoms using user information. The proposed system can establish the integrative control system of viral diseases by the prediction module of community outbreak and spread of viral diseases.

Utilization of Host Cell Chromosome Conformation by Viral Pathogens: Knowing When to Hold and When to Fold

Though viruses have their own genomes, many depend on the nuclear environment of their hosts for replication and survival. A substantial body of work has therefore been devoted to understanding how viral and eukaryotic genomes interact. Recent advances in chromosome conformation capture technologies have provided unprecedented opportunities to visualize how mammalian genomes are organized and, by extension, how packaging of nuclear DNA impacts cellular processes. Recent studies have indicated that some viruses, upon entry into host cell nuclei, produce factors that alter host chromatin topology, and thus, impact the 3D organization of the host genome. Additionally, a variety of distinct viruses utilize host genome architectural factors to advance various aspects of their life cycles. Indeed, human gammaherpesviruses, known for establishing long-term reservoirs of latent infection in B lymphocytes, utilize 3D principles of genome folding to package their DNA and establish latency in host cells. This manipulation of host epigenetic machinery by latent viral genomes is etiologically linked to the onset of B cell oncogenesis. Small DNA viruses, by contrast, are tethered to distinct cellular sites that support virus expression and replication. Here, we briefly review the recent findings on how viruses and host genomes spatially communicate, and how this impacts virus-induced pathology.

The first versatile human iPSC-based model of ectopic virus induction allows new insights in RNA-virus disease

A detailed description of pathophysiological effects that viruses exert on their host is still challenging. For the first time, we report a highly controllable viral expression model based on an iPS-cell line from a healthy human donor. The established viral model system enables a dose-dependent and highly localized RNA-virus expression in a fully controllable environment, giving rise for new applications for the scientific community.

The Genome Segments of Bluetongue Virus Differ in Copy Number in a Host-Specific Manner

ABSTRACT Genome segmentation is mainly thought to facilitate reassortment. Here, we show that segmentation can also allow differences in segment abundance in populations of bluetongue virus (BTV). BTV has a genome consisting in 10 segments, and its cycle primarily involves periodic alternation between ruminants and Culicoides biting midges. We have developed a reverse transcription-quantitative PCR (RT-qPCR) approach to quantify each segment in wild BTV populations sampled in both ruminants and midges during an epizootic. Segment frequencies deviated from equimolarity in all hosts. Interestingly, segment frequencies were reproducible and distinct between ruminants and biting midges. Beyond a putative regulatory role in virus expression, this phenomenon could lead to different evolution rates between segments. IMPORTANCE The variation in viral gene frequencies remains a largely unexplored aspect of within-host genetics. This phenomenon is often considered to be specific to multipartite viruses. Multipartite viruses have segmented genomes, but in contrast to segmented viruses, their segments are each encapsidated alone in a virion. A main hypothesis explaining the evolution of multipartism is that, compared to segmented viruses, it facilitates the regulation of segment abundancy, and the genes the segments carry, within a host. These differences in gene frequencies could allow for expression regulation. Here, we show that wild populations of a segmented virus, bluetongue virus (BTV), also present unequal segment frequencies. BTV cycles between ruminants and Culicoides biting midges. As expected from a role in expression regulation, segment frequencies tended to show specific values that differed between ruminants and midges. Our results expand previous knowledge on gene frequency variation and call for studies on its role and conservation beyond multipartite viruses.