Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics
Ebola virus (EBOV) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. Here, we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cells during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance.
By quantifying intracellular viral RNA, we identify molecular determinants of tropism among circulating immune cells and examine temporal dynamics in viral and host gene expression. Within infected cells, EBOV downregulates STAT1 mRNA and interferon signaling, and it upregulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating pathways the virus manipulates for its replication. This study sheds light on EBOV tropism, replication dynamics, and elicited immune response and provides a framework for characterizing host-virus interactions under maximum containment. Dengue virus (DENV) infection is one of the most important infectious diseases in tropical and subtropical regions around the world.
Previously, we performed an initial phenotypic screening of 7,000 compounds using DENV type 2 (DENV2)-infected BHK-21 cells to identify small molecules which could inhibit virus replication. In this study, we describe two novel compounds with anti-DENV2 activity, tentatively named Compound-X and Compound-Y. Both compounds possess a quinolone skeleton, and the EC50s of Compound-X and Compound-Y against DENV2 were 3.9 μM and 9.2 μM, respectively.
Based on a DENV replicon assay, it was suggested that these compounds have anti-DENV2 activity by inhibition of a step in virus replication. Furthermore, using mutational analysis we obtained compounds-resistant to DENV2 infection and identified a mutation, V130A in the NS5 methyltransferase (MTase) domain.
However, these compounds did not inhibit MTase activity. In addition, incorporation of an additional NS1 N246D mutation with the NS5 V130A mutation in DENV2 resulted in recovery of viral replication and a further reduction of the sensitivity to the quinolone compounds by an unknown mechanism. Therefore further investigations are required to clarify the antiviral mechanisms of these quinolone compounds.
Evidence for interspecies transmission route of pseudorabies virus via virally contaminated fomites
Pseudorabies virus (PRV) is a zoonotic agent with a wide host range, causing significant economic losses in animal husbandry and potential public health risk globally. The causative agent has recently gained attention due to the inter-species transmission among different species of animals, even human beings.
Although PRV’s prevalence is found in many species of animals, regardless of whether the strain involved is a vaccine, classical or variant, few lines of evidence for the viral transmission route are available. Here, we reported that viral contamination is associated with the inter-species transmission of PRV.
We found that PRV contamination was widely distributed in the environment of pig farms, that viral distribution in the environment is associated with the implementation of biosecurity measures, and that PRV could transmit from pigs to dogs through virally contaminated fomites. Collectively, our findings provide a basis for understanding the ecology and transmission route of PRV and underscore the importance of implementing biosecurity measures to control this disease.
Single-Cell Profiling of Ebola Virus Disease In Vivo Reveals Viral and Host Dynamics
Contemporary Understanding of Ebola and Zika Virus in Pregnancy
Understanding the pathophysiology, management, and prevention of emerging infectious diseases among pregnant women is imperative to achieve a successful response from the medical community. Ebola and Zika viruses represent infections with profound public health implications.
In particular, Ebola virus is associated with high case fatality and pregnancy and neonatal loss rates, while Zika virus has been associated with multiple congenital anomalies; these features present critical clinical dilemmas for management of pregnant and reproductive aged women. Influenza B viruses cause significant morbidity and mortality, particularly in children, but the awareness of their impact is often less than influenza A viruses partly due to their lack of pandemic potential. Here, we summarise the biology, epidemiology and disease burden of influenza B, and review existing data on available antivirals for its management.
There has long been uncertainty surrounding the clinical efficacy of neuraminidase inhibitors (NAIs) for influenza B treatment. In this article, we bring together the existing data on NAIs and discuss these alongside recent large randomised controlled trial data for the new polymerase inhibitor baloxavir in high-risk influenza B patients. Finally, we offer considerations for the clinical management of influenza B, with a focus on children and high-risk patients where disease burden is highest.
Description: Interleukin-8 (IL-8), also known as CXCL8, is an ELR-positive CXC family member chemokine produced by macrophages and other cell types such as epithelial cells. ELR-positive CXC chemokines such as IL-8 specifically induce the migration of neutrophils, and interact with chemokine receptors CXCR1 and CXCR2. Human IL-8 Recombinant Protein is purified interleukin-8 produced in yeast.
Human 8-Oxo-2'-Desoxiguanosina (8-Oxodguo) ELISA Kit
Description: DG-172 (hydrochloride) is an orally available inverse agonist of PPAR?/? with IC50 value of 27 nM [1]. Peroxisome proliferator-activated receptors (PPARs) are a member of the class II subset of nuclear receptors.
Description: DG-172 (hydrochloride) is an orally available inverse agonist of PPAR?/? with IC50 value of 27 nM [1]. Peroxisome proliferator-activated receptors (PPARs) are a member of the class II subset of nuclear receptors.
Description: DG-172 (hydrochloride) is an orally available inverse agonist of PPAR?/? with IC50 value of 27 nM [1]. Peroxisome proliferator-activated receptors (PPARs) are a member of the class II subset of nuclear receptors.
Description: DG-172 (hydrochloride) is an orally available inverse agonist of PPAR?/? with IC50 value of 27 nM [1]. Peroxisome proliferator-activated receptors (PPARs) are a member of the class II subset of nuclear receptors.
Description: DG-172 (hydrochloride) is an orally available inverse agonist of PPAR?/? with IC50 value of 27 nM [1]. Peroxisome proliferator-activated receptors (PPARs) are a member of the class II subset of nuclear receptors.
Description: 6-thio-dG is a nucleoside analogue [1], is a telomerase-mediated telomere disrupting compound [2]. It is an anti-cancer inhibitor [1]. Cancer cells were very sensitive to 6-thio-dG with observed IC50 values ranging from 0.43283.9 ?M, depending on cell types [3].
Description: 6-thio-dG is a nucleoside analogue [1], is a telomerase-mediated telomere disrupting compound [2]. It is an anti-cancer inhibitor [1]. Cancer cells were very sensitive to 6-thio-dG with observed IC50 values ranging from 0.43283.9 ?M, depending on cell types [3].
Description: 6-thio-dG is a nucleoside analogue [1], is a telomerase-mediated telomere disrupting compound [2]. It is an anti-cancer inhibitor [1]. Cancer cells were very sensitive to 6-thio-dG with observed IC50 values ranging from 0.43283.9 ?M, depending on cell types [3].
Rat 8-oxo-7,8-dihydro-2′-deoxyguanosine(8-oxodG)ELISA Kit
Description: A competitive ELISA for quantitative measurement of Human THSD7a in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive inhibition quantitative ELISA assay kit for detection of 8-Hydroxydeoxyguanosine (8-OHdG) in samples from serum, plasma or other biological fluids.
Description: A competitive inhibition quantitative ELISA assay kit for detection of 8-Hydroxydeoxyguanosine (8-OHdG) in samples from serum, plasma or other biological fluids.
Description: The pAAV-DJ/8 vector contains the rep and cap genes required to generated recombinant AAV of serotype DJ/8. Co-transfect with other packaging plasmids and an expression vector into 293 cells for AAV-DJ/8 packaging.
Description: The substance Cordycepin is a nucleoside antagonist. It is synthetically produced and has a purity of >98%. The pure substance is white powder which is May be dissolved in DMSO (25 mg/ml).
Description: The substance Cordycepin is a nucleoside antagonist. It is synthetically produced and has a purity of >98%. The pure substance is white powder which is May be dissolved in DMSO (25 mg/ml).
Description: The AAV Helper Free System produces recombinant AAV containing your gene of interest without the need to use a helper adenovirus. The adenoviral genes required for proper AAV packaging are provided in the pHelper plasmid (E2A, E4 and VA RNA) or in the 293 packaging cells (E1).
Description: The AAV Helper Free System produces recombinant AAV containing your gene of interest without the need to use a helper adenovirus. The adenoviral genes required for proper AAV packaging are provided in the pHelper plasmid (E2A, E4 and VA RNA) or in the 293 packaging cells (E1). AAV Helper Free Complete Expression Systems are available for native serotypes 1 through 6, as well as the novel AAV-DJ and AAV-DJ/8. The AAV-DJ system provides a hybrid capsid created by DNA shuffling technology combining 8 different native serotypes: AAV-2, AAV-4, AAV-5, AAV-8, AAV-9, avian AAV, bovine AAV, and caprine AAV. The result is a highly infectious vector that can transduce a wide variety of cells and tissues at significantly higher rates than AAV-2. AAV-DJ/8 was created by making a point mutation in the heparin binding domain of AAV-DJ. Recombinant AAV produced from the AAV-DJ/8 system closely resembles AAV-8 and AAV-9 in its ability to infect heart and brain tissues.
Description: The AAV Helper Free System produces recombinant AAV containing your gene of interest without the need to use a helper adenovirus. The adenoviral genes required for proper AAV packaging are provided in the pHelper plasmid (E2A, E4 and VA RNA) or in the 293 packaging cells (E1). AAV Helper Free Complete Expression Systems are available for native serotypes 1 through 6, as well as the novel AAV-DJ and AAV-DJ/8. The AAV-DJ system provides a hybrid capsid created by DNA shuffling technology combining 8 different native serotypes: AAV-2, AAV-4, AAV-5, AAV-8, AAV-9, avian AAV, bovine AAV, and caprine AAV. The result is a highly infectious vector that can transduce a wide variety of cells and tissues at significantly higher rates than AAV-2. AAV-DJ/8 was created by making a point mutation in the heparin binding domain of AAV-DJ. Recombinant AAV produced from the AAV-DJ/8 system closely resembles AAV-8 and AAV-9 in its ability to infect heart and brain tissues.
Description: The AAV Helper Free System produces recombinant AAV containing your gene of interest without the need to use a helper adenovirus. The adenoviral genes required for proper AAV packaging are provided in the pHelper plasmid (E2A, E4 and VA RNA) or in the 293 packaging cells (E1). AAV Helper Free Complete Expression Systems are available for native serotypes 1 through 6, as well as the novel AAV-DJ and AAV-DJ/8. The AAV-DJ system provides a hybrid capsid created by DNA shuffling technology combining 8 different native serotypes: AAV-2, AAV-4, AAV-5, AAV-8, AAV-9, avian AAV, bovine AAV, and caprine AAV. The result is a highly infectious vector that can transduce a wide variety of cells and tissues at significantly higher rates than AAV-2. AAV-DJ/8 was created by making a point mutation in the heparin binding domain of AAV-DJ. Recombinant AAV produced from the AAV-DJ/8 system closely resembles AAV-8 and AAV-9 in its ability to infect heart and brain tissues.
Description: P.fluorescens HCP Standards Set, A-F by Cygnus Technologies is available in Europe via Gentaur.
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Using joint species distribution modelling, we attribute the non-random virus occurrence patterns primarily to differences among host genotypes and local population context. Our results show that intraspecific variation among host genotypes may play a large, previously unquantified role in pathogen community structure.
