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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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
This report summarizes the lectures held at the meeting and highlights advances in the field.
Source: Antiviral Therapy - Category: Virology Source Type: research
This report summarizes the lectures held at the meeting and highlights advances in the field. PMID: 30597184 [PubMed - as supplied by publisher]
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
ler After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014–2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therap...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
Publication date: 24 July 2018Source: Cell Reports, Volume 24, Issue 4Author(s): Mariano Sanchez-Lockhart, Daniel S. Reyes, Jeanette C. Gonzalez, Karla Y. Garcia, Erika C. Villa, Bradley P. Pfeffer, John C. Trefry, Jeffrey R. Kugelman, Margaret L. Pitt, Gustavo F. PalaciosSummaryDevelopment of an effective vaccine became a worldwide priority after the devastating 2013–2016 Ebola disease outbreak. To qualitatively profile the humoral response against advanced filovirus vaccine candidates, we developed Domain Programmable Arrays (DPA), a systems serology platform to identify epitopes targeted after vaccination or filov...
Source: Cell Reports - Category: Cytology Source Type: research
Publication date: March 2018Source: Acta Pharmaceutica Sinica B, Volume 8, Issue 2Author(s): Qing Chen, Ke Tang, Xiaoyu Zhang, Panpan Chen, Ying GuoAbstractFiloviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in v...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research
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