IL-4/IL-13 polarization of macrophages enhances Ebola virus glycoprotein-dependent infection

by Kai J. Rogers, Bethany Brunton, Laura Mallinger, Dana Bohan, Kristina M. Sevcik, Jing Chen, Natalie Ruggio, Wendy Maury BackgroundEbolavirus (EBOV) outbreaks, while sporadic, cause tremendous morbidity and mortality. No therapeutics or vaccines are currently licensed; however, a vaccine has shown promise in clinical trials. A critical step towards development of effective therapeutics is a better understanding of factors that govern host susceptibility to this pathogen. As macrophages are an important cell population targeted during virus replication, we explore the effect of cytokine polarization on macrophage infection. Methods/Main findingsWe utilized a BSL2 EBOV model virus, infectious, recombinant vesicular stomatitis virus encoding EBOV glycoprotein (GP) (rVSV/EBOV GP) in place of its native glycoprotein. Macrophages polarized towards a M2-like anti-inflammatory state by combined IL-4 and IL-13 treatment were more susceptible to rVSV/EBOV GP, but not to wild-type VSV (rVSV/G), suggesting that EBOV GP-dependent entry events were enhanced by these cytokines. Examination of RNA expression of known surface receptors that bind and internalize filoviruses demonstrated that IL-4/IL-13 stimulated expression of the C-type lectin receptor DC-SIGN in human macrophages and addition of the competitive inhibitor mannan abrogated IL-4/IL-13 enhanced infection. Two murine DC-SIGN-like family members, SIGNR3 and SIGNR5, were upregulated by IL-4/IL-13 in murine macrophages, but only S...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research

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Authors: Asad A, Aamir A, Qureshi NE, Bhimani S, Jatoi NN, Batra S, Ochani RK, Abbasi MK, Tariq MA, Diwan MN Abstract Marburg Virus (MARV), along with the Ebola virus, belongs to the family of Filovirus and is cause of a lethal and severely affecting hemorrhagic fever. The Marburgvirus genus includes two viruses: MARV and Ravn. MARV has been recognized as one of utmost importance by the World Health Organization (WHO). The case fatality rate of the virus ranges from 24.0 to 88.0% which demonstrates its lethal nature and the need for its widespread information. The first case of the Marburgvirus disease (MARD) was r...
Source: Infezioni in Medicina - Category: Infectious Diseases Tags: Infez Med Source Type: research
Abstract Ebolaviruses and marburgviruses, members of the family Filoviridae, are known to cause fatal diseases often associated with hemorrhagic fever. Recent outbreaks of Ebola virus disease in West African countries and the Democratic Republic of the Congo have made clear the urgent need for the development of therapeutics and vaccines against filoviruses. Using replication-incompetent vesicular stomatitis virus (VSV) pseudotyped with the Ebola virus (EBOV) envelope glycoprotein (GP), we screened a chemical compound library to obtain new drug candidates that inhibit filoviral entry into target cells. We descover...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
in Waters Rebecca Shim William Dowling Jing Qin Ian Crozier Peter B. Jahrling Lisa E. Hensley Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013–2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Unti...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Discussions with the U.S. Food and Drug Administration (FDA) have taken place to define the required data set for filing US licensure. About Janssen’s Ebola Vaccine Regimen The Janssen preventive Ebola vaccine regimen, Ad26.ZEBOV and MVA-BN-Filo, utilizes a non-replicating viral vector strategy in which viruses – in this case adenovirus serotype 26 (Ad26) and Modified Vaccinia Virus Ankara (MVA) – are genetically modified so that they cannot replicate in human cells. In addition, these vectors carry the genetic code of several Ebola virus proteins in order to trigger an immune response.Janssen’s vac...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
Ebola virus is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single glycoprotein (GP). The virus is responsible for causing Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever (EHF), in humans. In particular, Bundibugyo (BDBV), Zaire (EBOV), and Sudan (SUDV) species have been associated with large outbreaks of EVD in Africa and reported case fatality rates of up to 90%. Transmission of Ebola virus to humans is not yet fully understood but is likely due to incidental exposure to infected animals. EVD spreads through human-to-human transmission, with infection re...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
Recent occurrences of filoviruses and the arenavirus Lassa virus (LASV) in overlapping endemic areas of Africa highlight the need for a prophylactic vaccine that would confer protection against all of these viruses that cause lethal hemorrhagic fever (HF). We developed a quadrivalent formulation of VesiculoVax that contains recombinant vesicular stomatitis virus (rVSV) vectors expressing filovirus glycoproteins and that also contains a rVSV vector expressing the glycoprotein of a lineage IV strain of LASV. Cynomolgus macaques were vaccinated twice with the quadrivalent formulation, followed by challenge 28 days after the b...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
by Brien K. Haun, Varney Kamara, Abigail S. Dweh, Kianalei Garalde-Machida, Saymajunkon S. E. Forkay, Melissa Takaaze, Madhuri Namekar, Teri Ann S. Wong, Ayesha E. R. Bell-Gam Woto, Peter Humphreys, Ophelia I. Weeks, Mosoka P. Fallah, John M. Berestecky, Vivek R. Nerurkar, Axel T. Lehrer Filoviruses such as Ebola virus (EBOV) cause outbreaks of viral hemorrhagic fevers for which no FDA-approved vaccines or drugs are available. The 2014–2016 EBOV outbreak in West Africa infected approximately 30,000 people, killing more than 11,000 and affecting thousands more in areas still suff ering from the effects of civil wars....
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract rVSVΔG-ZEBOV-GP vaccine is a live recombinant (r) vesicular stomatitis virus (VSV), where the VSV G protein is replaced with the Zaire Ebola virus (ZEBOV) glycoprotein (GP). For vaccine immunogenicity testing, clinical trial sera collected during an active ZEBOV outbreak underwent gamma irradiation (GI) before testing in biosafety level 2 laboratories to inactivate possible wild-type ZEBOV. Before irradiating pivotal trial samples, two independent studies evaluated the impact of GI (50 kGy) on binding ZEBOV-GP (ELISA) antibodies against rVSVΔG-ZEBOV-GP, using sera from a North American phase 1...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
Discussion Genome comparison of over 1,230 non-redundant, high quality EBOV full-length sequences within the Zaire lineage revealed both conserved and highly variable regions (Figure 1). The latter were concentrated in non-coding sequences, which were also more AT-rich than coding sequences, an observation that has also been made for other virus species, for instance Hepatitis B virus (González et al., 2018). The AT-content of coding sequences was most likely lower due to codon constraints, though we observe that the gene for RNA polymerase is richer in AT than the other EBOV genes. The analysis further identified ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Viruses, Vol. 11, Pages 137: Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir Viruses doi: 10.3390/v11020137 Authors: Jason E. Comer Olivier Escaffre Natasha Neef Trevor Brasel Terry L. Juelich Jennifer K. Smith Jeanon Smith Birte Kalveram David D. Perez Shane Massey Lihong Zhang Alexander N. Freiberg The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would fac...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
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